GeneTable

12. MOTOR NEURON DISEASES (Return to Disease group)

Disease phenotype

Item in this table

References

Gene symbol (chromosome)
protein

Spinal muscular atrophy , type I (Werdnig-Hoffman ) - (AR)

12.1

Gilliam TC, Brzustowicz LM, Castilla LH, Lehner T, Penchaszadeh GK, Daniels RJ, Byth BC, Knowles J, Hislop JE, Shapira Y, et al. Genetic homogeneity between acute and chronic forms of spinal muscular atrophy. Nature. 1990 Jun 28;345(6278):823-5. (1972783)

Melki J, Lefebvre S, Burglen L, Burlet P, Clermont O, Millasseau P, Reboullet S, Benichou B, Zeviani M, Le Paslier D, et al. De novo and inherited deletions of the 5q13 region in spinal muscular atrophies. Science. 1994 Jun 3;264(5164):1474-7. (7910982)

Bussaglia E, Clermont O, Tizzano E, Lefebvre S, Burglen L, Cruaud C, Urtizberea JA, Colomer J, Munnich A, Baiget M, et al. A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients. Nat Genet. 1995 Nov;11(3):335-7. (7581461)

Rodrigues NR, Owen N, Talbot K, Ignatius J, Dubowitz V, Davies KE. Deletions in the survival motor neuron gene on 5q13 in autosomal recessive spinal muscular atrophy. Hum Mol Genet. 1995 Apr;4(4):631-4. (7633412)

Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995 Jan 13;80(1):155-65. (7813012)

SMN1 (5q13)

Survival of motor neuron 1, telomeric

Spinal muscular atrophy, type II (intermediate) - (AR)

12.2

Matthijs, G.; Schollen, E.; Legius, E.; Devriendt, K.; Goemans, N.; Kayserili, H.; Apak, M. Y.; Cassiman, J.-J. : Unusual molecular findings in autosomal recessive spinal muscular atrophy. J. Med. Genet. 33: 409-474, 1996. (8733053)

Samilchuk, E.; D'Souza, B.; Bastaki, L. : Deletion analysis of the SMN and NAIP genes in Kuwaiti patients with spinal muscular atrophy. Hum. Genet. 98: 524-527, 1996. (8882869)

SMN1 (5q13)

Survival of motor neuron 1, telomeric

Spinal muscular atrophy, type III (Kugelberg-Welander) - (AR)

12.3

Melki J, Abdelhak S, Sheth P, Bachelot MF, Burlet P, Marcadet A, Aicardi J, Barois A, Carriere JP, Fardeau M, et al. Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q. Nature. 1990 Apr 19;344(6268):767-8. (1970420)

Brzustowicz LM, Lehner T, Castilla LH, Penchaszadeh GK, Wilhelmsen KC, Daniels R, Davies KE, Leppert M, Ziter F, Wood D, et al. Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3. Nature. 1990 Apr 5;344(6266):540-1. (2320125)

SMN1 (5q13)

Survival of motor neuron 1, telomeric

Spinal muscular atrophy, type IV, adult form - (AR)

12.4

Brahe, C.; Servidei, S.; Zappata, S.; Ricci, E.; Tonali, P.; Neri, G. : Genetic homogeneity between childhood-onset and adult-onset autosomal recessive spinal muscular atrophy. Lancet 346: 741-742, 1995. (7658877)

Clermont, O.; Burlet, P.; Lefebvre, S.; Burglen, L.; Munnich, A.; Melki, J. : SMN gene deletions in adult-onset spinal muscular atrophy. (Letter) Lancet 346: 1712-1713, 1995. (8551862)

SMN1 (5q13)

Survival of motor neuron 1, telomeric

Spinal muscular atrophy with congenital bone fractures 1 - (AR)

12.5

Knierim E, Hirata H, Wolf NI, Morales-Gonzalez S, Schottmann G, Tanaka Y, Rudnik-Schöneborn S, Orgeur M, Zerres K, Vogt S, van Riesen A, Gill E, Seifert F, Zwirner A, Kirschner J, Goebel HH, Hübner C, Stricker S, Meierhofer D, Stenzel W, Schuelke M. Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures. Am J Hum Genet. 2016 Mar 3;98(3):473-89. doi: 10.1016/j.ajhg.2016.01.006. (26924529)

TRIP4 (15q22.31)

Thyroid hormone receptor interactor 4

Spinal muscular atrophy with congenital bone fractures 2 - (AR)

12.6

ASCC1 (10q22.1)

Activating signal cointegrator 1 complex subunit 1

Spinal muscular atrophy with progressive myoclonic epilepsy - (AR)

12.7

Zhou, J., Tawk, M., Tiziano, F. D., Veillet, J., Bayes, M., Nolent, F., Garcia, V., Servidei, S., Bertini, E., Castro-Giner, F., Renda, Y., Carpentier, S., Andrieu-Abadie, N., Gut, I., Levade, T., Topaloglu, H., Melki, J. Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1. Am. J. Hum. Genet. 91: 5-14, 2012. (22703880)

ASAH1 (8p22)

N-acylsphingosine amidohydrolase (acid ceramidase) 1

Spinal muscular atrophy and cerebellar hypoplasia - (AR)

12.8

Boczonadi, V., Muller, J. S., Pyle, A., Munkley, J., Dor, T., Quartararo, J., Ferrero, I., Karcagi, V., Giunta, M., Polvikoski, T., Birchall, D., Princzinger, A., and 15 others. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nature Commun. 5: 4287, 2014. Note: Electronic Article. (24989451)

EXOSC8 (13q13.1)

Exosome component 8

Pontocerebellar hypoplasia, type 1D - (AR)

12.9

Burns, D. T., Donkervoort, S., Muller, J. S., Knierim, E., Bharucha-Goebel, D., Faqeih, E. A., Bell, S. K., Alfaifi, A. Y., Monies, D., Millan, F., Retterer, K., Dyack, S., and 18 others. Variants in EXOSC9 disrupt the RNA exosome and result in cerebellar atrophy with spinal motor neuronopathy. Am. J. Hum. Genet. 102: 858-873, 2018. [PubMed: 29727687, (29727687)

EXOSC9 (4q27 )

Exosome component 9

Spinal Muscular Atrophy type IV related to CAPN1 - (AR)

12.10

Perez-Siles G, Ellis M, Ashe A, Grosz B, Vucic S, Kiernan MC, Morris KA, Reddel SW, Kennerson ML. A Compound Heterozygous Mutation in Calpain 1 Identifies a New Genetic Cause for Spinal Muscular Atrophy Type 4 (SMA4). Front Genet. 2022 Jan 19;12:801253. doi: 10.3389/fgene.2021.801253. PMID: 35126465; PMCID: PMC8807693 (35126465)

CAPN1 (11q13.1)

Calpain 1

Scapuloperoneal spinal muscular atrophy - (AD)

12.11

Isozumi, K.; DeLong, R.; Kaplan, J.; Deng, H.-X.; Iqbal, Z.; Hung, W.-Y.; Wilhelmsen, K. C.; Hentati, A.; Pericak-Vance, M. A.; Siddique, T. : Linkage of scapuloperoneal spinal muscular atrophy to chromosome 12q24.1-q24.31. Hum. Molec. Genet. 5: 1377-1382, 1996. (20037587)

Deng, H.-X., Klein, C. J., Yan, J., Shi, Y., Wu, Y., Fecto, F., Yau, H.-J., Yang, Y., Zhai, H., Siddique, N., Hedley-Whyte, E. T., Delong, R., Martina, M, Dyck, P. J., Siddique, T. Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4. Nature Genet. 42: 165-169, 2010. (8872481)

TRPV4 (12q23-q24)

Transient receptor potential cation channel, subfamily V, member 4

12.12

Giunta M., Edvardson S., XuY., et al. Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy. Hum Mol Genet 2016 (27193168)

RBM7 (11q23.2)

RNA binding motif protein 7

Neuropathy, distal hereditary motor, autosomal recessive 1 - (AR)

12.13

Grohmann K, Wienker TF, Saar K, Rudnik-Schoneborn S, Stoltenburg-Didinger G, Rossi R, Novelli G, Nurnberg G, Pfeufer A, Wirth B, Reis A, Zerres K, Hubner C. Diaphragmatic spinal muscular atrophy with respiratory distress is heterogeneous, and one form Is linked to chromosome 11q13-q21. Am J Hum Genet. 1999 Nov;65(5):1459-62. No abstract available. (10521314)

IGHMBP2 (11q13.2-q13.4)

Immunoglobulin mu binding protein 2

Neuropathy, distal hereditary motor, autosomal recessive 2 - (AR)

12.14

Christodoulou K, Zamba E, Tsingis M, Mubaidin A, Horani K, Abu-Sheik S, El-Khateeb M, Kyriacou K, Kyriakides T, Al-Qudah AK, Middleton L. A novel form of distal hereditary motor neuronopathy maps to chromosome 9p21.1-p12. Ann Neurol. 2000 Dec;48(6):877-84. (11117544)

Li, X., Hu, Z., Liu, L., Xie, Y., Zhan, Y., Zi, X., Wang, J., Wu, L., Xia, K., Tang, B., Zhang, R. A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy. Neurology 84: 2430-2437, 2015. (26078401)

SIGMAR1 (9p13.3)

Sigma non-opioid intracellular receptor 1

Neuropathy, distal hereditary motor, autosomal recessive 3 - (AR)

12.15

Viollet L, Zarhrate M, Maystadt I, Estournet-Mathiaut B, Barois A, Desguerre I, Mayer M, Chabrol B, LeHeup B, Cusin V, Billette De Villemeur T, Bonneau D, Saugier-Veber P, Touzery-De Villepin A, Delaubier A, Kaplan J, Jeanpierre M, Feingold J, Munnich A. Refined genetic mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.3 and evidence of linkage disequilibrium in European families. Eur J Hum Genet. 2004 Jun;12(6):483-8. (15054395)

? - (11q13)

Neuropathy, distal hereditary motor, autosomal recessive 4 - (AR)

12.16

Maystadt I, Zarhrate M, Leclair-Richard D, Estournet B, Barois A, Renault F, Routon MC, Durand MC, Lefebvre S, Munnich A, Verellen-Dumoulin C, Viollet L. A gene for an autosomal recessive lower motor neuron disease with childhood onset maps to 1p36. Neurology. 2006 Jul 11;67(1):120-4. Epub 2006 May 25. (17564964)

Maystadt I, Rezs²∂hazy R, Barkats M, Duque S, Vannuffel P, Remacle S, Lambert B, Najimi M, Sokal E, Munnich A, Viollet L, Verellen-Dumoulin C. The nuclear factor kappaB-activator gene PLEKHG5 is mutated in a form of autosomal recessive lower motor neuron disease with childhood onset. Am J Hum Genet. 2007 Jul;81(1):67-76. Epub 2007 May 16. (16728649)

PLEKHG5 (1p36)

Pleckstrin homology domain containing, family G (with RhoGef domain) member 5

12.17

Blumen, S. C., Astord, S., Robin, V., Vignaud, L., Toumi, N., Cieslik, A., Achiron, A., Carasso, R. L., Gurevich, M., Braverman, I., Blumen, N., Munich, A., Barkats, M., Viollet, L. A rare recessive distal hereditary motor neuropathy with HSJ1 chaperone mutation. Ann. Neurol. 71: 509-519, 2012. (22522442)

DNAJB2 (2q32-q34)

DnaJ (Hsp40) homolog, subfamily B, member 2

12.18

Schottmann, G., Seelow, D., Seifert, F., Morales-Gonzalez, S., Gill, E., von Au, K., von Moers, A., Stenzel, W., Schuelke, M. Recessive REEP1 mutation is associated with congenital axonal neuropathy and diaphragmatic palsy. Neurol. Genet. 1: e32, 2015. [PubMed: 27066569, images, related citations] [Full Text] (27066569)

REEP1 (2p11.2)

Receptor accessory protein 1

Neuropathy, hereditary motor, autosomal recessive 7 - (AR)

12.19

Deschauer, M., Hengel, H., Rupprich, K., Kreiss, M., Schlotter-Weigel, B., Grimmel, M., Admard, J., Schneider, I., Alhaddad, B., Gazou, A., Sturm, M., Vorgerd, M., and 15 others. Bi-allelic truncating mutations in VWA1 cause neuromyopathy. Brain 144: 574-583, 2021. [PubMed: 33459760, (33459760)

Pagnamenta, A. T., Kaiyrzhanov, R., Zou, Y., Da'as, S. I., Maroofian, R., Donkervoort, S., Dominik, N., Lauffer, M., Ferla, M. P., Orioli, A., Giess, A., Tucci, A., and 43 others. An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy. Brain 144: 584-600, 2021. [PubMed: 33559681 (33559681)

VWA1 (1p36.33)

Von Willebrand factor A domain-containing protein 1

Neuropathy, hereditary motor, autosomal recessive 8 - (AR)

12.20

Cortese, A., Zhu, Y., Rebelo, A. P., Negri, S., Courel, S., Abreu, L., Bacon, C. J., Bai, Y., Bis-Brewer, D. M., Bugiardini, E., Buglo, E., Danzi, M. C., and 41 others. Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Nature Genet. 52: 473-481, 2020. Note: Erratum: Nature Genet. 52: 640 only, 2020. (32367058)

SORD (15q21.1)

Sorbitol Dehydrogenase

Neuropathy, distal hereditary motor, autosomal recessive 9 - (AR)

12.21

Jacquier, A., Theuriet, J., Fontaine, F., Mosbach, V., Lacoste, N., Ribault, S., Risson, V., Carras, J., Coudert, L., Simonet, T., Latour, P., Stojkovic, T., Piard, J., Cosson, A., Lesca, G., Bouhour, F., Allouche, S., Puccio, H., Pegat, A., Schaeffer, L. Homozygous COQ7 mutation: a new cause of potentially treatable distal hereditary motor neuropathy. Brain 146: 3470-3483, 2023. [PubMed: 36454683, images, related citations] [Full Text] (36454683)

Liu, X., Wang, N., Chen, Y., Lv, W., Hong, J.-M., Xu, G.-R., Zhou, L.-Y., Chen, W.-J., Fan, D.-S., He, J. Biallelic variants in the COQ7 gene cause distal hereditary motor neuropathy in two Chinese families. Brain 146: e27-e30, 2023. [PubMed: 36758993, related citations] [Full Text] (36758993)

Smith, I. C., Pileggi, C. A., Wang, Y., Kernohan, K., Hartley, T., McMillan, H. J., Sampaio, M. L., Melkus, G., Woulfe, J., Parmar, G., Bourque, P. R., Breiner, A., and 11 others. Novel homozygous variant in COQ7 in siblings with hereditary motor neuropathy. Neurol. Genet. 9: e200048, 2023. [PubMed: 37077559, images, related citations] [Full Text] (37077559)

COQ7 (16p12.3)

Coenzyme Q7

Neuronopathy, distal hereditary motor, autosomal recessive - (AR)

12.22

Stoll M, Hooiling Teoh, James Lee, Stephen Reddel, Ying Zhu, Michael Buckley, Hugo Sampaio, Tony Roscioli, Michelle Farrar, Garth Nicholson. Novel motor phenotypes in patients with VRK1 mutations without pontocerebellar hypoplasia. Neurology Jul 2016, 87 (1) 65-70; DOI: 10.1212/WNL.0000000000002813 (27281532)

Li N, Wang L, Sun X, Lu Z, Suo X, Li J, Peng J, Peng R. A novel mutation in VRK1 associated with distal spinal muscular atrophy. J Hum Genet. 2019 Jan 7. doi: 10.1038/s10038-018-0553-5. (30617279)

VRK1 (14q32)

Vaccinia related kinase 1

12.23

Zhao H, Race V, Matthijs G, De Jonghe P, Robberecht W, Lambrechts D, Van Damme P. Exome sequencing reveals HINT1 mutations as a cause of distal hereditary motor neuropathy. Eur J Hum Genet. 2014 Jun;22(6):847-50. doi: 10.1038/ejhg.2013.231. Epub 2013 Oct 9. (24105373)

HINT1 (5q23.3)

Histidine triad nucleotide binding protein 1

Neuronopathy, distal hereditary motor, type I - (AD)

12.24

Gopinath S, Blair IP, Kennerson ML, Durnall JC, Nicholson GA. A novel locus for distal motor neuron degeneration maps to chromosome 7q34-q36. Hum Genet. 2007 Jun;121(5):559-64. Epub 2007 Mar 13. (17354000)

? - (7q34-q36)

Neuronopathy, distal hereditary motor, autosomal dominant 2 - (AD)

12.25

Timmerman, V., Raeymaekers, P., Nelis, E., De Jonghe, P., Muylle, L., Ceuterick, C., Martin, J.-J., Van Broeckhoven, C. Linkage analysis of distal hereditary motor neuropathy type II (distal HMN II) in a single pedigree. J. Neurol. Sci. 109: 41-48, 1992. (1517763)

HSPB8 (12q24.23)

Heat shock 27kDa protein 8

Neuronopathy, distal hereditary motor, autosomal dominant 3 - (AD)

12.26

Evgrafov, O. V.; Mersiyanova, I.; Irobi, J.; Van Den Bosch, L.; Dierick, I.; Leung, C. L.; Schagina, O.; Verpoorten, N.; Van Impe, K.; Fedotov, V.; Dadali, E.; Auer-Grumbach, M.; and 14 others : Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. Nature Genet. 36: 602-606, 2004. (15122254 )

HSPB1 (7q11.23)

Heat shock 27kDa protein 1

Neuronopathy, distal hereditary motor, autosomal dominant 4 - (AD)

12.27

Kolb, S. J., Snyder, P. J., Poi, E. J., Renard, E. A., Bartlett, A., Gu, S., Sutton, S., Arnold, W. D., Freimer, M. L., Lawson, V. H., Kissel, J. T., Prior, T. W. Mutant small heat shock protein B3 causes motor neuropathy: utility of a candidate gene approach. Neurology 74: 502-506, 2010. (20142617)

HSPB3 (5q11.2)

Heat shock 27kDa protein 3

Neuronopathy, distal hereditary motor, autosomal dominant 5 - (AD)

12.28

Christodoulou K, Kyriakides T, Hristova AH, Georgiou DM, Kalaydjieva L, Yshpekova B, Ivanova T, Weber JL, Middleton LT. Related Articles, Links Mapping of a distal form of spinal muscular atrophy with upper limb predominance to chromosome 7p. Hum Mol Genet. 1995 Sep;4(9):1629-32. (12690580)

Antonellis A, Ellsworth RE, Sambuughin N, Puls I, Abel A, Lee-Lin SQ, Jordanova A, Kremensky I, Christodoulou K, Middleton LT, Sivakumar K, Ionasescu V, Funalot B, Vance JM, Goldfarb LG, Fischbeck KH, Green ED. Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V. Am J Hum Genet. 2003 May;72(5):1293-9. Epub 2003 Apr 10. (8541851)

GARS1 (7p15)

Glycyl-tRNA synthetase

Neuronopathy, distal hereditary motor, autosomal dominant 6 - (AD)

12.29

Sumner, C. J., d'Ydewalle, C., Wooley, J., Fawcett, K. A., Hernandez, D., Gardiner, A. R., Kalmar, B., Baloh, R. H., Gonzalez, M., Zuchner, S., Stanescu, H. C., Kleta, R., and 9 others. A dominant mutation in FBXO38 causes distal spinal muscular atrophy with calf predominance. Am. J. Hum. Genet. 93: 976-983, 2013. (24207122)

FBXO38 (5q32)

F-box protein 38

Neuronopathy, distal hereditary motor, autosomal dominant 7 - (ad)

12.30

McEntagart M, Norton N, Williams H, Teare MD, Dunstan M, Baker P, Houlden H, Reilly M, Wood N, Harper PS, Futreal PA, Williams N, Rahman N. Localization of the gene for distal hereditary motor neuronopathy VII (dHMN-VII) to chromosome 2q14. Am J Hum Genet. 2001 May;68(5):1270-6. Epub 2001 Apr 04. (11294660)

SLC5A7 (2q12.31)

Solute carrier family 5 (sodium/choline cotransporter), member 7

Neuronopathy, distal hereditary motor, autosomal dominant 8 - ( AD)

12.31

Van der Vleuten, A. J. W.; van Ravenswaaij-Arts, C. M. A.; Frijns, C. J. M.; Smits, A. P. T.; Hageman, G.; Padberg, G. W.; Kremer, H. : Localisation of the gene for a dominant congenital spinal muscular atrophy predominantly affecting the lower limbs to chromosome 12q23-q24. Europ. J. Hum. Genet. 6: 376-382, 1998. (20037587)

Auer-Grumbach, M., Olschewski, A., Papic, L., Kremer, H., McEntagart, M. E., Uhrig, S., Fischer, C., Frohlich, E., Balint, Z., Tang, B., Strohmaier, H., Lochmuller, H., and 13 others Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C. Nature Genet. 42: 160-164, 2010. (20037588)

TRPV4 (12q23-q24)

Transient receptor potential cation channel, subfamily V, member 4

Neuronopathy, distal hereditary motor, autosomal dominant 9 - (AD)

12.32

Tsai P.C., Soong B.W., Mademan I., Huang Y.H., Liu C.R., Hsiao C.T., et al. A recurrent WARS mutation is a novel cause of autosomal dominant distal hereditary motor neuropathy. Brain. 2017 Mar 22. (28369220)

WARS (14q32.2)

Tryptophanyl-tRNA synthetase

Neuronopathy, distal hereditary motor, autosomal dominant 10 - (AD)

12.33

Capuano, A., Bucciotti, F., Farwell, K. D., Davis, B. T., Mroske, C., Hulick, P. J., Weissman, S. M., Gao, Q., Spessotto, P., Colombatti, A., Doliana, R. Diagnostic exome sequencing identifies a novel gene, EMILIN1, associated with autosomal-dominant hereditary connective tissue disease. Hum. Mutat. 37: 84-97, 2016. [PubMed: 26462740, images, related citations] [Full Text] (26462740)

EMILIN1 (2p23.3)

Elastin microfibril interfacer 1

Neuronopathy, distal hereditary motor, autosomal dominant 11 - (AD)

12.34

Beijer D, Deconinck T, De Bleecker JL, Dotti MT, Malandrini A, Urtizberea JA, Zulaica M, López de Munain A, Asselbergh B, De Jonghe P, Baets J. Nonsense mutations in alpha-II spectrin in three families with juvenile onset hereditary motor neuropathy. Brain. 2019 Jul 22. pii: awz216. doi: 10.1093/brain/awz216. (31332438)

SPTAN1 (9q34.11)

Spectrin, alpha, nonerythrocytic 1

Neuronopathy, distal hereditary motor, autosomal dominant - (AD)

12.35

Beetz, C., Pieber, T. R., Hertel, N., Schabhuttl, M., Fischer, C., Trajanoski, S., Graf, E., Keiner, S., Kurth, I., Wieland, T., Varga, R.-E., Timmerman, V., Reilly, M. M., Strom, T. M., Auer-Grumbach, M. Exome sequencing identifies a REEP1 mutation involved in distal hereditary motor neuropathy type V. Am. J. Hum. Genet. 91: 139-145, 2012. (22703882)

REEP1 (2p11.2)

Receptor accessory protein 1

Neuronopathy, distal hereditary motor, autosomal dominant 13 - (AD)

12.36

Windpassinger, C.; Auer-Grumbach, M.; Irobi, J.; Patel, H.; Petek, E.; Horl, G.; Malli, R.; Reed, J. A.; Dierick, I.; Verpoorten, N.; Warner, T. T.; Proukakis, C.; Van den Bergh, P.; Verellen, C.; Van Maldergem, L.; Merlini, L.; De Jonghe, P.; Timmerman, V.; Crosby, A. H.; Wagner, K. : Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nature Genet. 36: 271-276, 2004. (14981520)

BSCL2 (11q12-q13.5)

Seipin

Neuronopathy, distal hereditary motor, autosomal dominant 14 - (AD)

12.37

Puls I, Jonnakuty C, LaMonte BH, Holzbaur EL, Tokito M, Mann E, Floeter MK, Bidus K, Drayna D, Oh SJ, Brown RH Jr, Ludlow CL, Fischbeck KH. Mutant dynactin in motor neuron disease. Nat Genet. 2003 Apr;33(4):455-6. Epub 2003 Mar 10. (12627231)

DCTN1 (2p13)

Dynactin 1

Dominant distal hereditary motor neuropathy - (AD)

12.38

Zhao Z, Hashiguchi A, Hu J, Sakiyama Y, Okamoto Y, Tokunaga S, Zhu L, Shen H, Takashima H. Alanyl-tRNA synthetase mutation in a family with dominant distal hereditary motor neuropathy. Neurology. 2012 May 22;78(21):1644-9. Epub 2012 May 9. (22573628)

AARS (16q22.1)

Alanyl-tRNA synthetase

Hereditary motor and sensory neuropathy V - (AD)

12.39

Muglia, M., Magariello, A., Citrigno, L., Passamonti, L., Sprovieri, T., Conforti, F. L., Mazzei, R., Patitucci, A., Gabriele, A. L., Ungaro, C., Bellesi, M., Quattrone, A. A novel locus for dHMN with pyramidal features maps to chromosome 4q34.3-q35.2. Clin. Genet. 73: 486-491, 2008. (18336586)

? - (4q34.3-q35.2)

Spinal muscular atrophy, lower extremity-predominant, autosomal dominant 1 - (AD)

12.40

Harms, M. B., Ori-McKenney, K. M., Scoto, M., Tuck, E. P., Bell, S., Ma, D., Masi, S., Allred, P., Al-Lozi, M., Reilly, M. M., Miller, L. J., Jani-Acsadi, A., Pestronk, A., Shy, M. E., Muntoni, F., Vallee, R. B., Baloh, R. H. Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy. Neurology 78: 1714-1720, 2012. (20697106)

Harms, M. B., Allred, P., Gardner, R., Jr., Fernandes Filho, J. A., Florence, J., Pestronk, A., Al-Lozi, M., Baloh, R. H. Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32. Neurology 75: 539-546, 2010. (22459677)

DYNC1H1 (14q32.31)

Dynein, cytoplasmic 1, heavy chain 1

Spinal muscular atrophy, lower extremity-predominant, autosomal dominant 2A - (AD)

12.41

Peeters, K., Litvinenko, I., Asselbergh, B., Almeida-Souza, L., Chamova, T., Geuens, T., Ydens, E., Zimon, M., Irobi, J., De Vriendt, E., De Winter, V., Ooms, T., Timmerman, V., Tournev, I., Jordanova, A. Molecular defects in the motor adaptor BICD2 cause proximal spinal muscular atrophy with autosomal-dominant inheritance. Am. J. Hum. Genet. 92: 955-964, 2013. (23664116)

Oates, E. C., Rossor, A. M., Hafezparast, M., Gonzalez, M., Speziani, F., MacArthur, D. G., Lek, M., Cottenie, E., Scoto, M., Foley, A. R., Hurles, M., Houlden, H., and 15 others. Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia. Am. J. Hum. Genet. 92: 965-973, 2013. (23664119)

Neveling, K., Martinez-Carrera, L. A., Holker, I., Heister, A., Verrips, A., Hosseini-Barkooie, S. M., Gilissen, C., Vermeer, S., Pennings, M., Meijer, R., te Riele, M., Frijns, C. J. M., and 12 others. Mutations in BICD2, which encodes a golgin and important motor adaptor, cause congenital autosomal-dominant spinal muscular atrophy. Am. J. Hum. Genet. 92: 946-954, 2013. (23664120)

BICD2 (9q22.31)

Bicaudal D homolog 2 (Drosophila)

Spinal muscular atrophy, lower extremity-predominant, autosomal dominant 2B - (AD)

12.42

Ravenscroft, G., Di Donato, N., Hahn, G., Davis, M. R., Craven, P. D., Poke, G., Neas, K. R., Neuhann, T. M., Dobyns, W. B., Laing, N. G. Recurrent de novo BICD2 mutation associated with arthrogryposis multiplex congenita and bilateral perisylvian polymicrogyria. Neuromusc. Disord. 26: 744-748, 2016. (27751653)

BICD2 (9q22.31)

Bicaudal D homolog 2 (Drosophila)

Spinal muscular atrophy, late-onset, Finkel type - (AD)

12.43

Nishimura, A. L.; Mitne-Neto, M.; Silva, H. C. A.; Oliveira, J. R. M.; Vainzof, M.; Zatz, M. : A novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13. J. Med. Genet. 41: 315-320, 2004. (15060112)

VAPB (7p15)

Vesicle-associated membrane protein-associated protein B and C

Spinal muscular atrophy, Jokela type - (AD)

12.44

Penttilä S, Jokela M, Hackman P, Maija Saukkonen A, Toivanen J, Udd B. Autosomal dominant late-onset spinal motor neuronopathy is linked to a new locus on chromosome 22q11.2-q13.2. Eur J Hum Genet. 2012 Nov;20(11):1193-6. doi: 10.1038/ejhg.2012.76. Epub 2012 Apr 25. (22535186)

Muller K., Andersen P.M., Hubers A., et al. Two novel mutations in conserved codons indicate that CHCHD10 is a gene associated with motor neuron disease. (Letter). Brain 2014;137:e309 (25113787)

CHCHD10 (22q11.2-q13.2)

Coiled-coil-helix-coiled-coil-helix domain containing 10

Neuronopathy, Distal hereditary motor related to SYT2 - (AD)

12.45

Montes-Chinea NI, Guan Z, Coutts M, Vidal C, Courel S, Rebelo AP, Abreu L, Zuchner S, Littleton JT, Saporta MA. Identification of a new SYT2 variant validates an unusual distal motor neuropathy phenotype. Neurol Genet. 2018 Oct 22;4(6):e282. doi: 10.1212/NXG.0000000000000282. eCollection 2018 Dec. (30533528)

SYT2 (1q32.1)

Synaptotagmin II

Neuronopathy, Distal hereditary motor related to GBF1 - (AD)

12.46

Mendoza-Ferreira N, Karakaya M, Cengiz N, Beijer D, Brigatti KW, Gonzaga-Jauregui C, Fuhrmann N, Hölker I, Thelen MP, Zetzsche S, Rombo R, Puffenberger EG, De Jonghe P, Deconinck T, Zuchner S, Strauss KA, Carson V, Schrank B, Wunderlich G, Baets J, Wirth B. De Novo and Inherited Variants in GBF1 are Associated with Axonal Neuropathy Caused by Golgi Fragmentation. Am J Hum Genet. 2020 Oct 1;107(4):763-777. doi: 10.1016/j.ajhg.2020.08.018. Epub 2020 Sep 15. (32937143)

GBF1 (10q24.32)

Golgi-specific brefeldin-A resistance factor 1

Spinal and bulbar muscular atrophy, X-linked, 1 (Kennedy disease) - (XR)

12.47

Fischbeck KH, Ionasescu V, Ritter AW, Ionasescu R, Davies K, Ball S, Bosch P, Burns T, Hausmanowa-Petrusewicz I, Borkowska J, et al. Localization of the gene for X-linked spinal muscular atrophy. Neurology. 1986 Dec;36(12):1595-8. (3466055)

La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature. 1991 Jul 4;352(6330):77-9. (2062380)

AR (Xq11.2-q12)

Androgen receptor

Spinal muscular atrophy, distal, X-linked, 2 - (XR)

12.48

Ramser, J., Ahearn, M. E., Lenski, C., Yariz, K. O., Hellebrand, H., von Rhein, M., Clark, R. D., Schmutzler, R. K., Lichtner, P., Hoffman, E. P., Meindl, A., Baumbach-Reardon, L. Rare missense and synonymous variants in UBE1 are associated with X-linked infantile spinal muscular atrophy. Am. J. Hum. Genet. 82: 188-193, 2008 (18179898)

UBA1 (Xp11.23)

Ubiquitin-activating enzyme 1

Spinal muscular atrophy, distal, X-linked, 3 - (XR)

12.49

Takata RI, Speck Martins CE, Passosbueno MR, Abe KT, Nishimura AL, Da Silva MD, Monteiro A Jr, Lima MI, Kok F, Zatz M. A new locus for recessive distal spinal muscular atrophy at Xq13.1-q21. J Med Genet. 2004 Mar;41(3):224-9. No abstract available. (14985388)

Kennerson ML, Nicholson GA, Kaler SG, Kowalski B, Mercer JF, Tang J, Llanos RM, Chu S, Takata RI, Speck-Martins CE, Baets J, Almeida-Souza L, Fischer D, Timmerman V, Taylor PE, Scherer SS, Ferguson TA, Bird TD, De Jonghe P, Feely SM, Shy ME, Garbern JY. Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy. Am J Hum Genet. 2010 Mar 12;86(3):343-52. Epub 2010 Feb 18. (20170900)

ATP7A (Xq13-q21)

ATPase, Cu++ transporting, alpha polypeptide

Spinal muscular atrophy with respiratory distress (SMARD) - (XR)

12.50

Stembalska A, Rydzanicz M, Walas W, Gasperowicz P, Pollak A, Pienkowski VM, Biela M, Klaniewska M, Gamrot Z, Gronska E, Ploski R, Smigiel R. Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene. Genes (Basel). 2022 Apr 21;13(5):725. doi: 10.3390/genes13050725. PMID: 35627110; PMCID: PMC9142081. (35627110)

LAS1L (Xq12)

Las1-like ribosome biogenesis factor

Amyotrophic lateral sclerosis 1 (dominant) - (AD)

12.51

Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng HX, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993 Mar 4;362(6415):59-62. Erratum in: Nature. 1993 Jul 22;364(6435):362. (8446170)

Siddique T, Figlewicz DA, Pericak-Vance MA, Haines JL, Rouleau G, Jeffers AJ, Sapp P, Hung WY, Bebout J, McKenna-Yasek D, et al. Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group. Neurology. 1996 Jun;46(6):1507-14. Review. (2020294)

Siddique, T.; Deng, H.-X. : Genetics of amyotrophic lateral sclerosis. Hum. Molec. Genet. 5: 1465-1470, 1996. (8875253)

SOD1 (21q22.1)

Superoxide dismutase 1, soluble

Amyotrophic lateral sclerosis 1 (recessive) - (AR)

12.52

Andersen, P. M.; Nilsson, P.; Ala-Hurula, V.; Keranen, M.-L.; Tarvainen, I.; Haltia, T.; Nilsson, L.; Binzer, M.; Forsgren, L.; Marklund, S. L. : Amyotrophic lateral sclerosis associated with homozygosity for an asp90-to-ala mutation in CuZn-superoxide dismutase. Nature Genet. 10: 61-66, 1995. (7647793)

SOD1 (21q22.1)

Superoxide dismutase 1, soluble

Amyotrophic lateral sclerosis 2 juvenile - (AR)

12.53

Hentati A, Bejaoui K, Pericak-Vance MA, Hentati F, Speer MC, Hung WY, Figlewicz DA, Haines J, Rimmler J, Ben Hamida C, et al. Linkage of recessive familial amyotrophic lateral sclerosis to chromosome 2q33-q35. Nat Genet. 1994 Jul;7(3):425-8. (7920663)

ALS2 (2q33.2)

Alsin Rho guanine nucleotide exchange factor 2

Amyotrophic lateral sclerosis 3 - (AR)

12.54

Hand, C. K.; Khoris, J.; Salachas, F.; Gros-Louis, F.; Simoes Lopes, A. A.; Mayeux-Portas, V.; Brewer, C. G.; Brown, R. H., Jr.; Meininger, V.; Camu, W.; Rouleau, G. A. : A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q. Am. J. Hum. Genet. 70: 251-256, 2002. Note: Erratum: Am. J. Hum. Genet. 71: 1007 only, 2002. (11706389)

? - (18q21)

Amyotrophic lateral sclerosis 4 - (AD)

12.55

Chance, P. F.; Rabin, B. A.; Ryan, S. G.; Ding, Y.; Scavina, M.; Crain, B.; Griffin, J. W.; Cornblath, D. R. : Linkage of the gene for an autosomal dominant form of juvenile amyotrophic lateral sclerosis to chromosome 9q34. Am. J. Hum. Genet. 62: 633-640, 1998. (9497266)

Chen, Y.-Z.; Bennett, C. L.; Huynh, H. M.; Blair, I. P.; Puls, I.; Irobi, J.; Dierick, I.; Abel, A.; Kennerson, M. L.; Rabin, B. A.; Nicholson, G. A.; Auer-Grumbach, M.; Wagner, K.; De Jonghe, P.; Griffin, J. W.; Fischbeck, K. H.; Timmerman, V.; Cornblath, D. R.; Chance, P. F. : DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am. J. Hum. Genet. 74: 1128-1135, 2004. (15106121)

SETX (9q34.13)

Senataxin

Amyotrophic lateral sclerosis 5 - (AD)

12.56

Hentati, A.; Ouahchi, K.; Pericak-Vance, M. A.; Nijhawan, D.; Ahmad, A.; Yang, Y.; Rimmler, J.; Hung, W.-Y.; Schlotter, B.; Ahmed, A.; Ben Hamida, M.; Hentati, F.; Siddique, T. : Linkage of a commoner form of recessive amyotrophic lateral sclerosis to chromosome 15q15-q22 markers. Neurogenetics 2: 55-60, 1998. (20110243)

Orlacchio A., Babalini C., Borreca A., et al. SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis. Brain 2010;133:591–8 (9933301)

SPG11 (15q21.1)

SPG11 vesicle trafficking associated, Spatacsin

Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia - (AD)

12.57

Sapp, P. C.; Hosler, B. A.; McKenna-Yasek, D.; Chin, W.; Gann, A.; Genise, H.; Gorenstein, J.; Huang, M.; Sailer, W.; Scheffler, M.; Valesky, M.; Haines, J. L.; Pericak-Vance, M.; Siddique, T.; Horvitz, H. R.; Brown, R. H., Jr. : Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis. Am. J. Hum. Genet. 73: 397-403, 2003. (12830400)

Abalkhail, H.; Mitchell, J.; Habgood, J.; Orrell, R.; de Belleroche, J. : A new familial amyotrophic lateral sclerosis locus on chromosome 16q12.1-16q12.2. Am. J. Hum. Genet. 73: 383-389, 2003. (12858291)

Kwiatkowski TJ, Jr., Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE and Brown RH, Jr. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009;323:1205-8. (19251627)

Vance, C.; Rogelj, B.; Hortobagyi, T.; De Vos, K. J.; Nishimura, A. L.; Sreedharan, J.; Hu, X.; Smith, B.; Ruddy, D.; Wright, P.; Ganesalingam, J.; Williams, K. L.; and 10 others : Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323: 1208-1211, 2009. (19251628)

FUS (16q12)

Fusion (involved in t(12;16) in malignant liposarcoma)

Amyotrophic lateral sclerosis 7 - (AD)

12.58

? - (20p13)

Amyotrophic lateral sclerosis 8 - (AD)

12.59

Nishimura, A. L.; Mitne-Neto, M.; Silva, H. C. A.; Richieri-Costa, A.; Middleton, S.; Cascio, D.; Kok, F.; Oliveira, J. R. M.; Gillingwater, T.; Webb, J.; Skehel, P.; Zatz, M. : A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am. J. Hum. Genet. 75: 822-831, 2004. (15060112)

VAPB (7p15)

Vesicle-associated membrane protein-associated protein B and C

Amyotrophic lateral sclerosis 9 - (AD)

12.60

Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J, Morrison KE, Green A, Acharya KR, Brown RH, Jr. and Hardiman O. ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Nat Genet 2006;38:411-3. Pub Med ID : 16501576 (16501576)

Wu D, Yu W, Kishikawa H, Folkerth RD, Iafrate AJ, Shen Y, Xin W, Sims K and Hu GF. Angiogenin loss-of-function mutations in amyotrophic lateral sclerosis. Ann Neurol 2007;62:609-17. (17886298)

ANG (14q11.2)

Angiogenin

Amyotrophic lateral sclerosis 10, with or without frontotemporal dementia - (AD)

12.61

Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G and Shaw CE. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008;319:1668-72. (18309045)

TARDBP (1p36.2)

TAR DNA binding protein

Amyotrophic lateral sclerosis 11 - (AD)

12.62

Chow, C. Y., Landers, J. E., Bergren, S. K., Sapp, P. C., Grant, A. E., Jones, J. M., Everett, L., Lenk, G. M., McKenna-Yasek, D. M., Weisman, L. S., Figlewicz, D., Brown, R. H., Meisler, M. H. Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. Am. J. Hum. Genet. 84: 85-88, 2009 (19118816)

FIG4 (6q21)

Sac domain-containing inositol phosphatase 3

Amyotrophic lateral sclerosis 12, with or without frontotemporal dementia - (AD, AR)

12.63

Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., Kinoshita, Y., Kamada, M., Nodera, H., Suzuki, H., Komure, O., Matsuura, S., and 15 others. Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465: 223-226, 2010. (20428114)

OPTN (10p14)

Optineurin

Amyotrophic lateral sclerosis 13, susceptibility to - (AD)

12.64

Elden, A. C., Kim, H.-J., Hart, M. P., Chen-Plotkin, A. S., Johnson, B. S., Fang, X., Armakola, M., Geser, F., Greene, R., Lu, M. M., Padmanabhan, A., Clay-Falcone, D., and 11 others. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466: 1069-1075, 2010. (21670397)

Van Damme, P., Veldink, J. H., van Blitterswijk, M., Corveleyn, A., van Vught, P. W. J., Thijs, V., Dubois, B., Matthijs, G., van den Berg, L. H., Robberecht, W. Expanded ATXN2 CAG repeat size in ALS identifies genetic overlap between ALS and SCA2. Neurology 76: 2066-2072, 2011. (20740007)

Daoud, H., Belzil, V., Martins, S., Sabbagh, M., Provencher, P., Lacomblez, L., Meininger, V., Camu, W., Dupre, N., Dion, P. A., Rouleau, G. A. Association of long ATXN2 CAG repeat sizes with increased risk of amyotrophic lateral sclerosis. Arch. Neurol. 68: 739-742, 2011. (21562247)

ATXN2 (12q24.12)

Ataxin 2

Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia - (AD)

12.65

Johnson, J. O., Mandrioli, J., Benatar, M., Abramzon, Y., Van Deerlin, V. M., Trojanowski, J. Q., Gibbs, J. R., Brunetti, M., Gronka, S., Wuu, J., Ding, J., McCluskey, L., and 25 others. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 68: 857-864, 2010. Note: Erratum: Neuron 69: 397 only, 2011. (21145000)

VCP (9p13-p12)

Valosin-containing protein

Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia - (AD)

12.66

Deng, H.-X., Chen, W., Hong, S.-T., Boycott, K. M., Gorrie, G. H., Siddique, N., Yang, Y., Fecto, F., Shi, Y., Zhai, H., Jiang, H., Hirano, M., and 11 others. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 477: 211-215, 2011. (21857683)

UBQLN2 (Xp11.21)

Ubiquilin 2

Amyotrophic lateral sclerosis 16, juvenile - (AR)

12.67

Al-Saif, A., Al-Mohanna, F., Bohlega, S. A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Ann. Neurol. 70: 913-919, 2011. (21842496)

SIGMAR1 (9p13.3)

Sigma non-opioid intracellular receptor 1

Amyotrophic lateral sclerosis 17 - (AD)

12.68

Parkinson, N., Ince, P. G., Smith, M. O., Highley, R., Skibinski, G., Andersen, P. M., Morrison, K. E., Pall, H. S., Hardiman, O., Collinge, J., Shaw, P. J., Disher, E. M. C., MRC Proteomics in ALS Study and the FReJA Consortium. ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology 67: 1074-1077, 2006. (16807408)

Cox, L. E., Ferraiuolo, L., Goodall, E. F., Heath, P. R., Higginbottom, A., Mortiboys, H., Hollinger, H. C., Hartley, J. A., Brockington, A., Burness, C. E., Morrison, K. E., Wharton, S. B., Grierson, A. J., Ince, P. G., Kirby, J., Shaw, P. J. Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS). PLoS One 5: e9872, 2010. Note: Electronic Article. (20352044)

CHMP2B (3p11.2)

Charged multivesicular body protein 2B

Amyotrophic lateral sclerosis 18 - (AD)

12.69

Wu, C.-H., Fallini, C., Ticozzi, N., Keagle, P. J., Sapp, P. C., Piotrowska, K., Lowe, P., Koppers, M., McKenna-Yasek, D., Baron, D. M., Kost, J. E., Gonzalez-Perez, P., and 26 others. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488: 499-503, 2012. (22801503)

PFN1 (17p13.2)

Profilin 1

Amyotrophic lateral sclerosis 19 - (AD)

12.70

Takahashi Y., Fukuda Y., Yoshimura J., Toyoda A., Kurppa K., Moritoyo T., et al. ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19. Am. J. Hum. Genet. 93: 900-905, 2013. (24119685)

ERBB4 (2q34)

V-ERB-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 4

Amyotrophic lateral sclerosis 20 - (AD)

12.71

Kim, H. J., Kim, N. C., Wang, Y.-D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., and 25 others. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495: 467-473, 2013. (23455423)

HNRNPA1 (12q13.13)

Heterogeneous nuclear ribonucleoprotein A1

Amyotrophic lateral sclerosis 21 - (AD)

12.72

Johnson, J. O., Pioro, E. P., Boehringer, A., Chia, R., Feit, H., Renton, A. E., Pliner, H. A., Abramzon, Y., Marangi, G., Winborn, B. J., Gibbs, J.R., Nalls, M. A., and 30 others. Mutations in the matrin 3 gene cause familial amyotrophic lateral sclerosis. Nature Neurosci. 17: 664-666, 2014. (24686783)

MATR3 (5q31)

Matrin 3

Amyotrophic lateral sclerosis 22, with or wothout frontotemporal dementia - (AD)

12.73

Smith B.N., Ticozzi N., Fallini C., Gkazi A.S., Topp S., Kenna K.P., et al. Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS. Neuron 84: 324-331, 2014. (25374358)

TUBA4A (2q35)

Tubulin, Alpha-4A

Amyotrophic lateral sclerosis 23 - (AD)

12.74

Smith, B. N., Topp, S. D., Fallini, C., Shibata, H., Chen, H.-J., Troakes, C., King, A., Ticozzi, N., Kenna, K. P., Soragia-Gkazi, A., Miller, J. W., Sato, A., and 44 others. Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis. Sci. Transl. Med. 9: eaad9157, 2017. Note: Electronic Article. (28469040)

ANXA11 (10q23.3)

Annexin A11

12.75

Brenner, D., Muller, K., Wieland, T., Weydt, P., Bohm, S., Lule, D., Hubers, A., Neuwirth, C., Weber, M., Borck, G., Wahlqvist, M., Danzer, K. M., Volk, A. E., Meitinger, T., Strom, T. M., Otto, M., Kassubek, J., Ludolph, A. C., Andersen, P. M., Weishaupt J. H. NEK1 mutations in familial amyotrophic lateral sclerosis. Brain 139: e28, 2016. Note: Electronic Article. (26945885)

Kenna, K. P., van Doormaal, P. T., Dekker, A. M., Ticozzi, N., Kenna, B. J., Diekstra, F. P., van Rheenen, W., van Eijk, K. R., Jones, A. R., Keagle, P., Shatunov, A., Sproviero, W., and 70 others. NEK1 variants confer susceptibility to amyotrophic lateral sclerosis. Nature Genet. 48: 1037-1042, 2016. (27455347)

NEK1 (4q33)

Never in motosis gene A-related kinase 1

Amyotrophic lateral sclerosis 25, susceptibility to - (AD)

12.76

Nicolas, A., Kenna, K. P., Renton, A. E., Ticozzi, N., Faghri, F., Chia, R., Dominov, J. A., Kenna, B. J., Nalls, M. A., Keagle, P., Rivera, A. M., van Rheenen, W., and 201 others. Genome-wide analyses identify KIF5A as a novel ALS gene. Neuron 97: 1268-1283, 2018. [PubMed: 29566793, (29566793)

KIF5A (12q13.13)

Kinesin family member 5A

Amyotrophic lateral sclerosis 28 - (AD)

12.77

Kume, K., Kurashige, T., Muguruma, K., Morino, H., Tada, Y., Kikumoto, M., Miyamoto, T., Akutsu, S. N., Matsuda, Y., Matsuura, S., Nakamori, M., Nishiyama, A., and 18 others. CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis. Am. J. Hum. Genet. 110: 1086-1097, 2023. [PubMed: 37339631, related citations] [Full Text] (37339631)

LRP12 (8q22.3)

Low density lipoprotein receptor-related protein 12

Susceptibility to amyotrophic lateral sclerosis related to NEFH - (AD)

12.78

Al-Chalabi, A., Andersen, P. M., Nilsson, P., Chioza, B., Andersson, J. L., Russ, C., Shaw, C. E., Powell, J. F., Leigh, P. N. Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum. Molec. Genet. 8: 157-164, 1999. (9931323)

NEFH (22q12.2)

Neurofilament, heavy polypeptide

Amyotrophic lateral sclerosis related to peripherin, susceptibility to - (AD)

12.79

Leung CL, He CZ, Kaufmann P, Chin SS, Naini A, Liem RK, Mitsumoto H, Hays AP. A pathogenic peripherin gene mutation in a patient with amyotrophic lateral sclerosis. Brain Pathol. 2004 Jul;14(3):290-6. (15322088)

Gros-Louis, F., Lariviere, R., Gowing, G., Laurent, S., Camu, W., Bouchard, J.-P., Meininger, V., Rouleau, G. A., Julien, J.-P. A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis. J. Biol. Chem. 279: 45951-45956, 2004. (15446584)

PRPH (12q13.12)

Peripherin

Amyotrophic lateral sclerosis related to dynactin 1, susceptibility to - (AD)

12.80

Munch C, Rosenbohm A, Sperfeld AD et al. Heterozygous R1101K mutation of the DCTN1 gene in a family with ALS and FTD. Ann Neurol 2005;58:777-80 (16240349)

DCTN1 (2p13)

Dynactin 1

Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 - (AD)

12.81

Morita M, Al-Chalabi A, Andersen PM, Hosler B, Sapp P, Englund E, Mitchell JE, Habgood JJ, de Belleroche J, Xi J, Jongjaroenprasert W, Horvitz HR, Gunnarsson LG, Brown RH Jr. A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia. Neurology. 2006 Mar 28;66(6):839-44. Epub 2006 Jan 18. (21944778)

DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., Kouri, N., Wojtas, A., and 16 others. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72: 245-256, 2011. (16421333)

C9orf72 (9p21.2)

Chromosome 9 open reading frame 72

Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 - (AD)

12.82

Bannwarth, S., Ait-El-Mkadem, S., Chaussenot, A., Genin, E. C., Lacas-Gervais, S., Fragaki, K., Berg-Alonso, L., Kageyama, Y., Serre, V., Moore, D. G., Verschueren, A., Rouzier, C., and 11 others. A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement. Brain 137: 2329-2345, 2014. (24934289)

CHCHD10 (22q11.2-q13.2)

Coiled-coil-helix-coiled-coil-helix domain containing 10

Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 - (AD)

12.83

Fecto, F., Yan, J., Vemula, S. P., Liu, E., Yang, Y., Chen, W., Zheng, J. G., Shi, Y., Siddique, N., Arrat, H., Donkervoort, S., Ajroud-Driss, S., Sufit, R. L., Heller, S. L., Deng, H.-X., Siddique, T. SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. Arch. Neurol. 68: 1440-1446. (22084127)

SQSTM1 (5q35.3)

Sequestosome 1

Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 - (AD)

12.84

Cirulli, E. T., Lasseigne, B. N., Petrovski, S., Sapp, P. C., Dion, P. A., Leblond, C. S., Couthouis, J., Lu, Y.-F., Wang, Q., Krueger, B. J., Ren, Z., Keebler, J., and 60 others. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 347: 1436-1441, 2015. (25700176)

Freischmidt, A., Wieland, T., Richter, B., Ruf, W., Schaeffer, V., Muller, K., Marroquin, N., Nordin, F., Hubers, A., Weydt, P., Pinto, S., Press, R., and 28 others. Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nature Neurosci. 18: 631-636, 2015. (25803835)

TBK1 (12q14.2)

Tank-binding kinase 1

Amyotrophic lateral sclerosis - (AD)

12.85

Ni J, Liu Z, Li W, Yuan Y, Huang L, Hu Y, Liu P, Hou X, Jiao B, Li J, Shen L, Jiang H, Tang B, Wang J. Rare, pathogenic variants in LRP10 are associated with amyotrophic lateral sclerosis in patients from mainland China. Neurobiol Aging. 2021 Jan;97:145.e17-145.e22. doi: 10.1016/j.neurobiolaging.2020.06.013. Epub 2020 Jun 25. PMID: 32690342. (32690342)

LRP10 (14q11.2)

Low Density Lipoprotein Receptor-Related Protein 10

Amyotrophic lateral sclerosis - (AD)

12.86

Mohassel P, Donkervoort S, Lone MA, Nalls M, Gable K, Gupta SD, Foley AR, Hu Y, Saute JAM, Moreira AL, Kok F, Introna A, Logroscino G, Grunseich C, Nickolls AR, Pourshafie N, Neuhaus SB, Saade D, Gangfuß A, Kölbel H, Piccus Z, Le Pichon CE, Fiorillo C, Ly CV, Töpf A, Brady L, Specht S, Zidell A, Pedro H, Mittelmann E, Thomas FP, Chao KR, Konersman CG, Cho MT, Brandt T, Straub V, Connolly AM, Schara U, Roos A, Tarnopolsky M, Höke A, Brown RH, Lee CH, Hornemann T, Dunn TM, Bönnemann CG. Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. Nat Med. 2021 Jul;27(7):1197-1204. doi: 10.1038/s41591-021-01346-1. Epub 2021 May 31. PMID: 34059824. (34059824)

SPTLC1 (9q22.2)

Serine palmitoyltransferase subunit 1

Lethal Congenital Contracture Syndrome 1 - (AR)

12.87

M²§kel²§-Bengs P, J²§rvinen N, Vuopala K, Suomalainen A, Ignatius J, Sipil²§ M, Herva R, Palotie A, Peltonen L. Assignment of the disease locus for lethal congenital contracture syndrome to a restricted region of chromosome 9q34, by genome scan using five affected individuals. Am J Hum Genet. 1998 Aug;63(2):506-16. (18204449)

Nousiainen HO, Kestil²§ M, Pakkasj²§rvi N, Honkala H, Kuure S, Tallila J, Vuopala K, Ignatius J, Herva R, Peltonen L. Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease. Nat Genet. 2008 Feb;40(2):155-7. Epub 2008 Jan 20. (9683599)

GLE1 (9q34.11)

GLE1 RNA export mediator homolog (yeast)

Lethal Congenital Contracture Syndrome 2 - (AR)

12.88

Narkis G, Ofir R, Manor E, Landau D, Elbedour K, Birk OS. Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway. Am J Hum Genet. 2007 Sep;81(3):589-95. Epub 2007 Jul 24. (17701904)

ERBB3 (12q13)

V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)

Lethal Congenital Contracture Syndrome 3 - (AR)

12.89

Narkis G, Ofir R, Landau D, Manor E, Volokita M, Hershkowitz R, Elbedour K, Birk OS. Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway. Am J Hum Genet. 2007 Sep;81(3):530-9. Epub 2007 Jul 24. (17701898)

PIP5K1C (19p13.3)

Phosphatidylinositol-4-phosphate 5-kinase, type I, gamma

Lethal Congenital Contracture Syndrome 4 - (AR)

12.90

Markus, B., Narkis, G., Landau, D., Birk, R. Z., Cohen, I., Birk, O. S. Autosomal recessive lethal congenital contractural syndrome type 4 (LCCS4) caused by a mutation in MYBPC1. Hum. Mutat. 33: 1435-1438, 2012. (22610851)

MYBPC1 (12q23.2)

Myosin-binding proteinC, slow type

Lethal Congenital Contracture Syndrome 5 - (AR)

12.91

Koutsopoulos, O. S., Kretz, C., Weller, C. M., Roux, A., Mojzisova, H., Bohm, J., Koch, C., Toussaint, A., Heckel, E., Stemkens, D., ter Horst, S. A. J., Thibault, C., Koch, M., Mehdi, S. Q., Bijlsma, E. K., Mandel, J.-L., Vermot, J., Laporte, J. Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome. Europ. J. Hum. Genet. 21: 637-642, 2013. (23092955)

DNM2 (19p13.2)

Dynamin 2

Lethal Congenital Contracture Syndrome 6 - (AR)

12.92

Patel, N., Smith, L. L., Faqeih, E., Mohamed, J., Gupta, V. A., Alkuraya, F. S. ZBTB42 mutation defines a novel lethal congenital contracture syndrome (LCCS6). Hum. Molec. Genet. 23: 6584-6593, 2014. (25055871)

ZBTB42 (14q32.33)

Zinc finger and BTB domain-containing protein 42

Lethal Congenital Contracture Syndrome 7 - (AR)

12.93

Laquerriere, A., Maluenda, J., Camus, A., Fontenas, L., Dieterich, K., Nolent, F., Zhou, J., Monnier, N., Latour, P., Gentil, D., Heron, D., Desguerres, I., and 48 others. Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects. Hum. Molec. Genet. 23: 2279-2289, 2014. (24319099)

Lakhani, S., Doan, R., Almureikhi, M., Partlow, J. N., Al Saffar, M., Elsaid, M. F., Alaaraj, N., Barkovich, A. J., Walsh, C. A., Ben-Omran, T. Identification of a novel CNTNAP1 mutation causing arthrogryposis multiplex congenita with cerebral and cerebellar atrophy. Europ. J. Med. Genet. 60: 245-249, 2017. (28254648)

CNTNAP1 (17q21.2)

Contactin-Associated Protein 1

Lethal Congenital Contracture Syndrome 8 - (AR)

12.94

Agolini E, Cherchi C, Bellacchio E, et al. Expanding the clinical and molecular spectrum of lethal congenital contracture syndrome 8 associated with biallelic variants of ADCY6. Clin Genet. 2020;97(4):649-654. doi:10.1111/cge.13691 (31846058)

ADCY6 (12q13.12)

Adenylate cyclase 6

Lethal Congenital Contracture Syndrome 9 - (AR)

12.95

Ravenscroft, G., Nolent, F., Rajagopalan, S., Meireles, A. M., Paavola, K. J., Gaillard, D., Alanio, E., Buckland, M., Arbuckle, S., Krivanek, M., Maluenda, J., Pannell, S., and 9 others. Mutations of GPR126 are responsible for severe arthrogryposis multiplex congenita. Am. J. Hum. Genet. 96: 955-961, 2015. (26004201)

ADGRG6 (6q24.2)

Adhesion G protein-coupled recptor G6

Lethal Congenital Contracture Syndrome 10 - (AR)

12.96

Casey, J. P., Brennan, K., Scheidel, N., McGettigan, P., Lavin, P. T., Carter, S., Ennis, S., Dorkins, H., Ghali, N., Blacque, O. E., McGee, M. M., Murphy, H., Lynch, S. A. Recessive NEK9 mutation causes a lethal skeletal dysplasia with evidence of cell cycle and ciliary defects. Hum. Molec. Genet. 25: 1824-1835, 2016. (26908619)

NEK9 (14q24.3)

Never in mitosis gene A-related kinase 9

Lethal Congenital Contracture Syndrome 11 - (AR)

12.97

Maluenda, J., Manso, C., Quevarec, L., Vivanti, A., Marguet, F., Gonzales, M., Guimiot, F., Petit, F., Toutain, A., Whalen, S., Grigorescu, R., Coeslier, A. D., Gut, M., Gut, I., Laquerriere, A., Devaux, J., Melki, J. Mutations in GLDN, encoding gliomedin, a critical component of the nodes of Ranvier, are responsible for lethal arthrogryposis. Am. J. Hum. Genet. 99: 928-933, 2016. (27616481)

GLDN (15q21.2)

Gliomedin

Lethal Congenital Contracture Syndrome related to TTN - (AR)

12.98

Chervinsky E, Khayat M, Soltsman S, Habiballa H, Elpeleg O, Shalev S. A homozygous TTN gene variant associated with lethal congenital contracture syndrome. Am J Med Genet A. 2018;176(4):1001-1005. doi:10.1002/ajmg.a.38639 (29575618)

TTN (2q31)

Titin

Spinal muscular atrophy with pontocerebellar hypoplasia, type 1b - (AR)

12.99

Rudnik-SchoÅNneborn S, Senderek J, Jen JC, et al. Pontocerebellar hypoplasia type 1: Clinical spectrum and relevance of EXOSC3 mutations. Neurology 2013; 80: 438–436 (23284067)

EXOSC3 (9p13.2)

Exosome component 3

Spinal muscular atrophy with pontocerebellar hypoplasia - (AR)

12.100

Renbaum P, Kellerman E, Jaron R, Geiger D, Segel R, Lee M, King MC, Levy-Lahad E. Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. Am J Hum Genet. 2009 Aug;85(2):281-9. Epub 2009 Jul 30. (19646678)

VRK1 (14q32)

Vaccinia related kinase 1

Pontocerebellar hypoplasia with spinal muscular atrophy - (AR)

12.101

Wan, J., Steffen, J., Yourshaw, M., Mamsa, H., Andersen, E., Rudnik-Shoneborn, S., Pope, K., Howell, K. B., McLean, C. A., Kornberg, A. J., Joseph, J., Lockhart, P. J., Zerres, K., Ryan, M. M., Nelson, S. F., Koehler, C. M., Jen, J. C. Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia. Brain 139: 2877-2890, 2016. (27543974)

SLC25A46 (5q22.1)

solute carrier family 25 member 46

Brown-Vialetto-van Laere syndrome 1 - (AR)

12.102

Bosch AM, Abeling NG, Ijlst L, Knoester H, van der Pol WL, Stroomer AE, Wanders RJ, Visser G, Wijburg FA, Duran M, Waterham HR. Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment. J Inherit Metab Dis. 2011 Feb;34(1):159-64. Epub 2010 Nov 26. (21110228)

Green P, Wiseman M, Crow YJ, Houlden H, Riphagen S, Lin JP, Raymond FL, Childs AM, Sheridan E, Edwards S, Josifova DJ. Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54. Am J Hum Genet. 2010 Mar 12;86(3):485-9. Epub 2010 Mar 4. (22740598)

Johnson JO, Gibbs JR, Megarbane A, Urtizberea JA, Hernandez DG, Foley AR, Arepalli S, Pandraud A, Simón-Sánchez J, Clayton P, Reilly MM, Muntoni F, Abramzon Y, Houlden H, Singleton AB. Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease. Brain. 2012 Sep;135(Pt 9):2875-82. Epub 2012 Jun 26. (20206331)

SLC52A3 (20p13)

Solute carrier family 52, riboflavin transporter, member 3

Brown-Vialetto-van Laere syndrome 2 - (AR)

12.103

SLC52A2 (8q24)

Solute carrier family 52, riboflavin transporter, member 2

Late onset spinal muscular atrophy related to HEXB - (AD)

12.104

Rattay TW SL, Wilhelm C, Synofzik M. Late adult-onset pure spinal muscular atrophy due to a compound HEXB macro-deletion. Amyotroph Lateral Scler Frontotemporal Degener. 2013;Jul 25. (23886397)

HEXB (5q13.3)

Hexosaminidase B

Spinal muscular atrophy, related to PRUNE1 - (AR)

12.105

Lacomino M, Fiorillo C, Torella A, Severino M, Broda P, Romano C, Falsaperla R, Pozzolini G, Minetti C, Striano P, Nigro V, Zara F. Spinal motor neuron involvement in a patient with homozygous PRUNE mutation. Eur J Paediatr Neurol. 2018 May;22(3):541-543. doi: 10.1016/j.ejpn.2017.12.005. Epub 2017 Dec 18. ( 293077)

PRUNE1 (1q21.3)

Prune exopolyphosphatase 1

Spinal muscular atrophy with pontocerebellar hypoplasia related to KIF26B - (AD)

12.106

Wojcik MH, Okada K, Prabhu SP, Nowakowski DW, Ramsey K, Balak C, Rangasamy S, Brownstein CA, Schmitz-Abe K, Cohen JS, Fatemi A, Shi J, Grant EP, Narayanan V, Ho HH, Agrawal PB. De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy. Am J Med Genet A. 2018 Aug 27. doi: 10.1002/ajmg.a.40493. (30151950)

KIF26B (1q44)

Kinesin family member 26B

Peripheral neuropathy, myopathy, hoarseness and hearing loss - (AD)

12.107

Choi BO, Kang SH, Hyun YS, Kanwal S, Park SW, Koo H, Kim SB, Choi YC, Yoo JH, Kim JW, Park KD, Choi KG, Kim SJ, Züchner S, Chung KW. A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14. Hum Mutat. 2011 Jun;32(6):669-77. doi: 10.1002/humu.21488. Epub 2011 Apr 7. PMID:21480433 (21480433)

MYH14 (19q13.33)

Myosin, heavy chain 14, non muscle

Lower motor neuron disease with respiratory failure related to MAPT - (AD)

12.108

Di Fonzo A, Ronchi D, Gallia F, Cribiù FM, Trezzi I, Vetro A, Della Mina E, Limongelli I, Bellazzi R, Ricca I, Micieli G, Fassone E, Rizzuti M, Bordoni A, Fortunato F, Salani S, Mora G, Corti S, Ceroni M, Bosari S, Zuffardi O, Bresolin N, Nobile-Orazio E1, Comi GP. Lower motor neuron disease with respiratory failure caused by a novel MAPT mutation. Neurology Jun 2014, 82 (22) 1990-1998; DOI: 10.1212/WNL.0000000000000476 (24808015)

MAPT (17q21.31 )

Microtubule associated protein Tau

Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development - (AR)

12.109

Schuurs-Hoeijmakers, J. H. M., Vulto-van Silfhout, A. T., Vissers, L. E. L. M., van de Vondervoort, I. I. G. M., van Bon, B. W. M., de Ligt, J., Gilissen, C., Hehir-Kwa, J. Y., Neveling, K., del Rosario, M., Hira, G., Reitano, S., and 19 others. Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing. J. Med. Genet. 50: 802-811, 2013. (24123876)

Ylikallio, E., Woldegebriel, R., Tumiati, M., Isohanni, P., Ryan, M. M., Stark, Z., Walsh, M., Sawyer, S. L., Bell, K. M., Oshlack, A., Lockhart, P. J., Shcherbii, M., and 17 others. MCM3AP in recessive Charcot-Marie-Tooth neuropathy and mild intellectual disability. Brain 140: 2093-2103, 2017. (28633435)

MCM3AP (21q22.3)

Minichromosome maintenance 3-associated protein

Inclusion body myopathy and brain white matter abnormalities - (AD)

12.110

Leoni TB, González-Salazar C, Rezende TJR, Hernández ALC, Mattos AHB, Coimbra Neto AR, da Graça FF, Gonçalves JPN, Martinez ARM, Taniguti L, Kitajima JP, Kok F, Rogério F, da Silva AMS, de Oliveira ALR, Zanoteli E, Nucci A, França MC Jr. A Novel Multisystem Proteinopathy Caused by a Missense ANXA11 Variant. Ann Neurol. 2021 Aug;90(2):239-252. doi: 10.1002/ana.26136. Epub 2021 Jun 14. PMID: 34048612 (34048612)

ANXA11 (10q23.3)

Annexin A11

Mitochondrial complex IV deficiency, nuclear type 11 - (AR)

12.111

Dong HL, Ma Y, Yu H, Wei Q, Li JQ, Liu GL, Li HF, Chen L, Chen DF, Bai G, Wu ZY. Bi-allelic loss of function variants in COX20 gene cause autosomal recessive sensory neuronopathy. Brain. 2021 Sep 4;144(8):2457-2470. doi: 10.1093/brain/awab135. PMID: 33751098 (33751098)

COX20 (1q44)

Cytochrome c Oxidase Assembly Factor COX20

Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures - (AR)

12.112

Danhauser, K., Alhaddad, B., Makowski, C., Piekutowska-Abramczuk, D., Syrbe, S., Gomez-Ospina, N., Manning, M. A., Kostera-Pruszczyk, A., Krahn-Peper, C., Berutti, R., Kovacs-Nagy, R., Gusic, M., and 24 others. Bi-allelic ADPRHL2 mutations cause neurodegeneration with developmental delay, ataxia, and axonal neuropathy. Am. J. Hum. Genet. 103: 817-825, 2018 (30388405)

Ghosh, S. G., Becker, K., Huang, H., Dixon-Salazar, T., Chai, G., Salpietro, V., Al-Gazali, L., Waisfisz, Q., Wang, H., Vaux, K. K., Stanley, V., Manole, A., and 27 others. Biallelic mutations in ADPRHL2, encoding ADP-ribosylhydrolase 3, lead to a degenerative pediatric stress-induced epileptic ataxia syndrome. Am. J. Hum. Genet. 103: 431-439, 2018. (30401461)

ADPRHL2 (1p34.3)

ADP-Ribosylhydrolase-Like 2

Spinobulbar muscular atrophy (SBMA) - (AD)

12.113

Radziwonik W, Elert-Dobkowska E, Tomczuk F, Wozniak A, Sobanska A, Stepniak I, Koziorowski D, Zaremba J, Su?ek A. C9orf72 hexanucleotide repeat expansion found in suspected spinobulbar muscular atrophy (SBMA). Neurol Neurochir Pol. 2022;56(3):276-280. doi: 10.5603/PJNNS.a2022.0039. Epub 2022 Jun 6. PMID: 35661131 (35661131)

C9orf72 (9p21.2)

Chromosome 9 open reading frame 72

GeneTable of Neuromuscular Disorders