3. CONGENITAL MYOPATHIES (Return to Disease group)
Disease phenotype
Item in this table
References
Gene symbol (chromosome)
protein
Nemaline myopathy 1 - (AD)
3.1
Laing NG, Majda BT, Akkari PA, Layton MG, Mulley JC, Phillips H, Haan EA, White SJ, Beggs AH, Kunkel LM, et al. Assignment of a gene (NEMI) for autosomal dominant nemaline myopathy to chromosome I. Am J Hum Genet. 1992 Mar;50(3):576-83. (1347195)
Laing NG, Wilton SD, Akkari PA, Dorosz S, Boundy K, Kneebone C, Blumbergs P, White S, Watkins H, Love DR, et al. A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy NEM1. Nat Genet. 1995 Jun;10(2):249. (7663526)
TPM3 (1q21.2)
Tropomyosin 3
Nemaline myopathy 2 - (AR)
3.2
Wallgren-Pettersson C, Avela K, Marchand S, Kolehmainen J, Tahvanainen E, Hansen FJ, Muntoni F, Dubowitz V, De Visser M, Van Langen IM, et al. A gene for autosomal recessive nemaline myopathy assigned to chromosome 2q by linkage analysis. Neuromuscul Disord. 1995 Nov;5(6):441-3. (10051637)
Pelin K, Hilpela P, Donner K, Sewry C, Akkari PA, Wilton SD, Wattanasirichaigoon D, Bang ML, Centner T, Hanefeld F, Odent S, Fardeau M, Urtizberea JA, Muntoni F, Dubowitz V, Beggs AH, Laing NG, Labeit S, de la Chapelle A, Wallgren-Pettersson C. Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2305-10. (12207937)
Wallgren-Pettersson, C.; Donner, K.; Sewry, C.; Bijlsma, E.; Lammens, M.; Bushby, K.; Giovannucci Uzielli, M. L.; Lapi, E.; Odent, S.; Akcoren, Z.; Topaloglu, H.; Pelin, K. : Mutations in the nebulin gene can cause severe congenital nemaline myopathy. Neuromusc. Disord. 12: 674-679, 2002. (16917880)
Lehtokari, V.-L.; Pelin, K.; Sandbacka, M.; Ranta, S.; Donner, K.; Muntoni, F.; Sewry, C.; Angelini, C.; Bushby, K.; Van den Bergh, P.; Iannaccone, S.; Laing, N. G.; Wallgren-Pettersson, C. : Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Hum. Mutat. 27: 946-956, 2006. (8580725)
NEB (2q22)
Nebulin
Nemaline myopathy 3 - (AD)
3.3
Nowak KJ, Wattanasirichaigoon D, Goebel HH, et al. Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy. Nat Genet 1999;23:208-212. (10508519)
ACTA1 (1q42.1)
Alpha actin, skeletal muscle
Nemaline myopathy 4 - (AD)
3.4
Donner K, Ollikainen M, Ridanpaa M, Christen HJ, Goebel HH, de Visser M, Pelin K, Wallgren-Pettersson C. Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy. Neuromuscul Disord. 2002 Feb;12(2):151-8. (11738357)
TPM2 (9p13)
Tropomyosin 2 (beta)
Nemaline myopathy 5 - (AR)
3.5
Johnston, J. J.; Kelley, R. I.; Crawford, T. O.; Morton, D. H.; Agarwala, R.; Koch, T.; Schaffer, A. A.; Francomano, C. A.; Biesecker, L. G. : A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am. J. Hum. Genet. 67: 814-821, 2000. (10952871)
TNNT1 (19q13.4)
Slow troponin T
Nemaline myopathy 6 - (AD)
3.6
Gommans, I. M. P.; Davis, M.; Saar, K.; Lammens, M.; Mastaglia, F.; Lamont, P.; van Duijnhoven, G.; ter Laak, H. J.; Reis, A.; Vogels, O. J. M.; Laing, N.; van Engelen, B. G. M.; Kremer, H. : A locus on chromosome 15q for a dominantly inherited nemaline myopathy with core-like lesions. Brain 126: 1545-1551, 2003 (12805120)
Sambuughin, N., Yau, K. S., Olive, M., Duff, R. M., Bayarsaikhan, M., Lu, S., Gonzalez-Mera, L., Sivadorai, P., Nowak, K. J., Ravenscroft, G., Mastaglia, F. L., North, K. N., and 9 others. Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause nemaline myopathy with cores. Am. J. Hum. Genet. 87: 842-847, 2010. (21109227)
KBTBD13 (15q22.31)
Kelch repeat and BTB (POZ) domain containing 13
Nemaline myopathy 7 - (AR)
3.7
Agrawal PB, Greenleaf RS, Tomczak KK, Lehtokari VL, Wallgren-Pettersson C, Wallefeld W, Laing NG, Darras BT, Maciver SK, Dormitzer PR, Beggs AH. Nemaline Myopathy with Minicores Caused by Mutation of the CFL2 Gene Encoding the Skeletal Muscle Actin-Binding Protein, Cofilin-2. Am J Hum Genet. 2007 Jan;80(1):162-7. (17160903)
CFL2 (14q12)
Cofilin 2 (muscle)
Nemaline myopathy 8 - (AR)
3.8
Ravenscroft, G., Miyatake, S., Lehtokari, V.-L., Todd, E. J., Vornanen, P., Yau, K. S., Hayashi, Y. K., Miyake, N., Tsurusaki, Y., Doi, H., Saitsu, H., Osaka, H., and 43 others. Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. Am. J. Hum. Genet. 93: 6-18, 2013. (23746549)
KLHL40 (2p22.1)
Kelch-like family member 40
Nemaline myopathy 9 - (AR)
3.9
Gupta, V. A., Ravenscroft, G., Shaheen, R., Todd, E. J., Swanson, L. C., Shiina, M., Ogata, K., Hsu, C., Clarke, N. F., Darras, B. T., Farrar, M. A., Hashem, A., and 18 others. Identification of KLHL41 mutations implicates BTB-kelch-mediated ubiquitination as an alternate pathway to myofibrillar disruption in nemaline myopathy. Am. J. Hum. Genet. 93: 1108-1117, 2013. (24268659)
KLHL41 (2q31.1)
Kelch-like family member 41
Nemaline myopathy 10 - (AR)
3.10
Yuen, M., Sandaradura, S. A., Dowling, J. J., Kostyukova, A. S., Moroz, N., Quinlan, K. G., Lehtokari, V.-L., Ravenscroft, G., Todd, E. J., Ceyhan-Birsoy, O., Gokhin, D. S., Maluenda, J., and 45 others. Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy. J. Clin. Invest. 124: 4693-4708, 2014. (25250574)
LMOD3 (3p14.1)
Leiomodin 3 (fetal)
Nemaline myopathy 11 - (AE)
3.11
Miyatake, S., Mitsuhashi, S., Hayashi, Y. K., Purevjav, E., Nishikawa, A., Koshimizu, E., Suzuki, M., Yatabe, K., Tanaka, Y., Ogata, K., Kuru, S., Shiina, M., and 11 others. Biallelic mutations in MYPN, encoding myopalladin, are associated with childhood-onset, slowly progressive nemaline myopathy. Am. J. Hum. Genet. 100: 169-178, 2017. (28017374)
Lornage X., Malfatti E., Chéraud C., Schneider R., (28220527)
MYPN (10q21.1)
Myopalladin
Klippel-Feil syndrome with Nemalin myopathy and facial dysmorphism - (AR)
3.12
Malfatti, E., Bohm, J., Lacene, E., Beuvin, M., Brochier, G., Romero, N. B., Laporte, J. A premature stop codon in MYO18B is associated with severe nemaline myopathy with cardiomyopathy. J. Neuromusc. Dis. 2: 219-227, 2015. (27858739)
MYO18B (22q12.1)
Myosin XVIIIB
Myopathy with nemaline bodies - (AR)
3.13
Nilipour Y, Nafissi S, Tjust AE, Ravenscroft G, Hossein Nejad Nedai H, Taylor RL, Varasteh V, Pedrosa Domellöf F, Zangi M, Tonekaboni SH, Olivé M, Kiiski K, Sagath L, Davis MR, Laing NG, Tajsharghi H. Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies. Eur J Neurol. 2018 Jun;25(6):841-847. doi: 10.1111/ene.13607. Epub 2018 Mar 26. (29498452)
RYR3 (15q13-q14)
Ryanodine receptor 3
Myopathy, congenital, with fiber-type disproportion 1 - (AD)
3.14
Nowak KJ, Wattanasirichaigoon D, Goebel HH, et al. Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy. Nat Genet 1999;23:208-212. (10508519)
Clarke, N. F.; North, K. N. : Congenital fiber type disproportion--30 years on. J. Neuropath. Exp. Neurol. 62: 977-989, 2003. (14575234)
Laing, N. G.; Clarke, N. F.; Dye, D. E.; Liyanage, K.; Walker, K. R.; Kobayashi, Y.; Shimakawa, S.; Hagiwara, T.; Ouvrier, R.; Sparrow, J. C.; Nishino, I.; North, K. N.; Nonaka, I. : Actin mutations are one cause of congenital fibre type disproportion. Ann. Neurol. 56: 689-694, 2004. (15468086)
ACTA1 (1q42.1)
Alpha actin, skeletal muscle
Myopathy, congenital, with fiber-type disproportion - (AR)
3.15
Clarke NF, Kidson W, Quijano-Roy S, Estournet B, Ferreiro A, Guicheney P, Manson JI, Kornberg AJ, Shield LK, North KN. SEPN1: associated with congenital fiber-type disproportion and insulin resistance. Ann Neurol. 2006 Mar;59(3):546-52. (16365872)
SELENON (1p36.13)
Selenoprotein N1
Myopathy congenital, with fiber-type disproportion - (AR)
3.16
Clarke, N. F.; North, K. N. : Congenital fiber type disproportion--30 years on. J. Neuropath. Exp. Neurol. 62: 977-989, 2003. (14575234)
TPM3 (1q21.2)
Tropomyosin 3
Myopathy, congenital, with fiber-type disproportion - (AR)
3.17
Clarke, N. F.; Kolski, H.; Dye, D. E.; Lim, E.; Smith, R. L. L.; Patel, R.; Fahey, M. C.; Bellance, R.; Romero, N. B.; Johnson, E. S.; Labarre-Vila, A.; Monnier, N.; Laing, N. G.; North, K. N. Mutations in TPM3 are a common cause of congenital fiber type disproportion. Ann. Neurol. 63: 329-337, 2008. (18300303)
RYR1 (19q13.1)
Ryanodine receptor 1 (skeletal)
Myopathy, congenital, with fiber-type disproportion - (AD)
3.18
Ortolano S, Tarrío R, Blanco-Arias P, Teijeira S, Rodríguez-Trelles F, García-Murias M, Delague V, Lévy N, Fernández JM, Quintáns B, Millán BS, Carracedo A, Navarro C, Sobrido MJ. A novel MYH7 mutation links congenital fiber type disproportion and myosin storage myopathy. Neuromuscul Disord. 2011 Apr;21(4):254-62. Epub 2011 Feb 1. (21288719)
MYH7 (14q12)
Myosin, heavy polypeptide 7, cardiac muscle, beta
Myopathy congenital, with fiber-type disproportion - (AR)
3.19
Weterman MA, Barth PG, van Spaendonck-Zwarts KY, Aronica E, Poll-The BT, Brouwer OF, van Tintelen JP, Qahar Z, Bradley EJ, de Wissel M, et al. 2013. Recessive MYL2 mutations cause infantile type I muscle fibre disease and cardiomyopathy. Brain 136: 282–293.doi:10.1093/brain/aws293 (31127036)
MYL2 (12q23-q24.3)
Myosin light chain 2
Myopathy, congenital, with fiber-type disproportion - (AR)
3.20
Vasli, N., Harris, E., Karamchandani, J., Bareke, E., Majewski, J., Romero, N. B., Stojkovic, T., Barresi, R., Tasfaout, H., Charlton, R., Malfatti, E., Bohm, J., and 13 others. Recessive mutations in the kinase ZAK cause a congenital myopathy with fibre type disproportion. Brain 140: 37-48, 2017 (27816943)
MAP3K20 (2q31.1)
Mitogen-activated protein kinase kinase 20
Myotubular myopathy, X-linked - (XR)
3.21
Thomas, N. S. T.; Williams, H.; Cole, G.; Roberts, K.; Clarke, A.; Liechti-Gallati, S.; Braga, S.; Gerber, A.; Meier, C.; Moser, H.; Harper, P. S. : X linked neonatal centronuclear/myotubular myopathy: evidence for linkage to Xq28 DNA marker loci. J. Med. Genet. 27: 284-287, 1990. (8640223)
Laporte J, Hu LJ, Kretz C, Mandel JL, Kioschis P, Coy JF, Klauck SM, Poustka A, Dahl N. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet. 1996 Jun;13(2):175-82. (10790201)
Laporte J, Guiraud-Chaumeil C, Vincent MC, Mandel JL, Tanner SM, Liechti-Gallati S, Wallgren-Pettersson C, Dahl N, Kress W, Bolhuis PA, Fardeau M, Samson F, Bertini E. Mutations in the MTM1 gene implicated in X-linked myotubular myopathy. ENMC International Consortium on Myotubular Myopathy. European Neuro-Muscular Center. Hum Mol Genet. 1997 Sep;6(9):1505-11. (2352256 )
Laporte, J.; Biancalana, V.; Tanner, S. M.; Kress, W.; Schneider, V.; Wallgren-Pettersson, C.; Herger, F.; Buj-Bello, A.; Blondeau, F.; Liechti-Gallati, S.; Mandel, J.-L. : MTM1 mutations in X-linked myotubular myopathy. Hum. Mutat. 15: 393-409, 2000. (9305655)
MTM1 (Xq28)
Myotubularin
Centronuclear myopathy 1 - (AD)
3.22
Robinson, R. L.; Brooks, C.; Brown, S. L.; Ellis, F. R.; Halsall, P. J.; Quinnell, R. J.; Shaw, M.-A.; Hopkins, P. M. : RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes. Hum. Mutat. 20: 88-97, 2002. (16227997)
Bitoun M, Maugenre S, Jeannet PY, Lacene E, Ferrer X, Laforet P, Martin JJ, Laporte J, Lochmuller H, Beggs AH, Fardeau M, Eymard B, Romero NB, Guicheney P. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet. 2005 Nov;37(11):1207-9. Epub 2005 Oct 16. (12124989)
DNM2 (19p13.2)
Dynamin 2
Centronuclear myopathy 2 - (AD)
3.23
Böhm J, Biancalana V, Malfatti E, Dondaine N, Koch C, Vasli N, Kress W, Strittmatter M, Taratuto AL, Gonorazky H, Laforêt P, Maisonobe T, Olivé M, Gonzalez-Mera L, Fardeau M, Carrière N, Clavelou P, Eymard B, Bitoun M, Rendu J, Fauré J, Weis J, Mandel JL, Romero NB, Laporte J. Adult-onset autosomal dominant centronuclear myopathy due to BIN1 mutations. Brain. 2014 Sep 25. pii: awu272. (25260562)
BIN1 (2q14)
Amphiphysin
Centronuclear myopathy related to RYR1 - (AR)
3.24
Wilmshurst JM, Lillis S, Zhou H, Pillay K, Henderson H, Kress W, M²ºller CR, Ndondo A, Cloke V, Cullup T, Bertini E, Boennemann C, Straub V, Quinlivan R, Dowling JJ, Al-Sarraj S, Treves S, Abbs S, Manzur AY, Sewry CA, Muntoni F, Jungbluth H. RYR1 mutations are a common cause of congenital myopathies with central nuclei. Ann Neurol. 2010 Nov;68(5):717-26. (20839240)
RYR1 (19q13.1)
Ryanodine receptor 1 (skeletal)
Centronuclear myopathy (CNM) related to TTN - (AD)
3.25
Ceyhan-Birsoy O, Agrawal PB, Hidalgo C, Schmitz-Abe K, DeChene ET, Swanson LC, Soemedi R, Vasli N, Iannaccone ST, Shieh PB, Shur N, Dennison JM, Lawlor MW, Laporte J, Markianos K, Fairbrother WG, Granzier H, Beggs AH. Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy. Neurology. 2013 Oct 1;81(14):1205-14. doi: 10.1212/WNL.0b013e3182a6ca62. Epub 2013 Aug 23. (23975875)
TTN (2q31)
Titin
Centronuclear myopathy 5 - (AR)
3.26
Agrawal PB, Pierson CR, Joshi M, Liu X, Ravenscroft G, Moghadaszadeh B, Talabere T, Viola M, Swanson LC, Halilo?lu G, Talim B, Yau KS, Allcock RJ, Laing NG, Perrella MA, Beggs AH. SPEG interacts with myotubularin, and its deficiency causes centronuclear myopathy with dilated cardiomyopathy. Am J Hum Genet. 2014 Aug 7;95(2):218-26. doi: 10.1016/j.ajhg.2014.07.004. Epub 2014 Jul 31. (25087613)
SPEG (2q35)
SPEG complex locus
Centronuclear myopathy 4 - (AD)
3.27
Majczenko K, Davidson AE, Camelo-Piragua S, Agrawal PB, Manfready RA, Li X, Joshi S, Xu J, Peng W, Beggs AH, Li JZ, Burmeister M, Dowling JJ. Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies. Eur J Neurol. 2018 Jun;25(6):841-847. doi: 10.1111/ene.13607. Epub 2018 Mar 26. (29498452)
CCDC78 (16p13.3)
Coiled-coil domain-containing protein 78
Central core disease, dominant - (AD)
3.28
Kausch K, Lehmann-Horn F, Janka M, Wieringa B, Grimm T, Muller CR. Evidence for linkage of the central core disease locus to the proximal long arm of human chromosome 19. Genomics. 1991 Jul;10(3):765-9. (1889818)
Zhang Y, Chen HS, Khanna VK, De Leon S, Phillips MS, Schappert K, Britt BA, Browell AK, MacLennan DH. A mutation in the human ryanodine receptor gene associated with central core disease. Nat Genet. 1993 Sep;5(1):46-50. (8220422)
Quane KA, Healy JM, Keating KE, Manning BM, Couch FJ, Palmucci LM, Doriguzzi C, Fagerlund TH, Berg K, Ording H, et al. Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. Nat Genet. 1993 Sep;5(1):51-5 (8220423)
RYR1 (19q13.1)
Ryanodine receptor 1 (skeletal)
Central core disease, recessive (transient multiminicore myopathy) - (AR)
3.29
Jungbluth, H.; Muller, C. R.; Halliger-Keller, B.; Brockington, M.; Brown, S. C.; Feng, L.; Chattopadhyay, A.; Mercuri, E.; Manzur, A. Y.; Ferreiro, A.; Laing, N. G.; Davis, M. R.; Roper, H. P.; Dubowitz, V.; Bydder, G.; Sewry, C. A.; Muntoni, F. : Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores. Neurology 59: 284-287, 2002. (12112081)
Ferreiro, A.; Monnier, N.; Romero, N. B.; Leroy, J.-P.; Bonnemann, C.; Haenggeli, C.-A.; Straub, V.; Voss, W. D.; Nivoche, Y.; Jungbluth, H.; Lemainque, A.; Voit, T.; Lunardi, J.; Fardeau, M.; Guicheney, P. : A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene. Ann. Neurol. 51: 750-759, 2002. (12136074)
RYR1 (19q13.1)
Ryanodine receptor 1 (skeletal)
Multiminicore disease with external ophtalmopegia - (AR)
3.30
Monnier N, Ferreiro A, Marty I, Labarre-Vila A, Mezin P, Lunardi J. A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia. Hum Mol Genet 2003; 12: 1171-8. (12719381)
Jungbluth H, Zhou H, Hartley L, Halliger-Keller B, Messina S, Longman C, Brockington M, Robb S A, Straub V, Voit T, Swash M, Ferreiro A, Bydder G, Sewry C A, Muller C, Muntoni F. Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene. Neurology 2005; 65: 1930-5. (16380615)
RYR1 (19q13.1)
Ryanodine receptor 1 (skeletal)
Multiminicore disease (MmD), classical form - (AR)
3.31
Ferreiro, A.; Quijano-Roy, S.; Pichereau, C.; Moghadaszadeh, B.; Goemans, N.; Bonnemann, C.; Jungbluth, H.; Straub, V.; Villanova, M.; Leroy, J.-P.; Romero, N. B.; Martin, J.-J.; Muntoni, F.; Voit, T.; Estournet, B.; Richard, P.; Fardeau, M.; Guicheney, P. : Mutations of the selenoprotein N gene, which is implicated in rigid spine muscular dystrophy, cause the classical phenotype of multiminicore disease: reassessing the nosology of early-onset myopathies. Am. J. Hum. Genet. 71: 739-749, 2002 (12192640)
Ferreiro, A.; Ceuterick-de Groote, C.; Marks, J. J.; Goemans, N.; Schreiber, G.; Hanefeld, F.; Fardeau, M.; Martin, J.-J.; Goebel, H. H.; Richard, P.; Guicheney, P.; Bonnemann, C. G. : Desmin-related myopathy with Mallory body-like inclusions is caused by mutations of the selenoprotein N gene. Ann. Neurol. 55: 676-686, 2004. (15122708)
SELENON (1p36.13)
Selenoprotein N1
Multiminicore disease (MmD) related to TTN - (AR)
3.32
Ge L, Fu X, Zhang W, Wang D, Wang Z, Yuan Y, Nonaka I, Xiong H. Recessive mutations in proximal I-band of TTN gene cause severe congenital multi-minicore disease without cardiac involvement. Neuromuscul Disord. 2019 May;29(5):350-357. doi: 10.1016/j.nmd.2019.03.007. Epub 2019 Mar 14. (31053406)
TTN (2q31)
Titin
Early onset myopathy, areflexia, respiratory distress and dysphagia - (AR)
3.33
Logan, C. V., Lucke, B., Pottinger, C., Abdelhamed, Z. A., Parry, D. A., Szymanska, K., Diggle, C. P., van Riesen, A., Morgan, J. E., Markham, G., Ellis, I., Manzur, A. Y., and 12 others. Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD). Nature Genet. 43: 1189-1192, 2011. (22101682)
MEGF10 (5q23.2)
Multiple EGF-like-domains 10
Recessive congenital myopathy with minicores - (AR)
3.34
Boyden, S. E., Mahoney, L. J., Kawahara, G., Myers, J. A., Mitsuhashi, S., Estrella, E. A., Duncan, A. R., Dey, F., DeChene, E. T., Blasko-Goehringer, J. M., Bonnemann, C. G., Darras, B. T., Mendell, J. R., Lidov, H. G. W., Nishino, I., Beggs, A. H., Kunkel, L. M., Kang, P. B. Mutations in the satellite cell gene MEGF10 cause a recessive congenital myopathy with minicores. Neurogenetics 13: 115-124, 2012. (22371254)
MEGF10 (5q23.2)
Multiple EGF-like-domains 10
Myopathy, myosin storage, autosomal dominant - (AD)
3.35
Bohlega, S.; Abu-Amero, S. N.; Wakil, S. M.; Carroll, P.; Al-Amr, R.; Lach, B.; Al-Sayed, Y.; Cupler, E. J.; Meyer, B. F. : Mutation of the slow myosin heavy chain rod domain underlies hyaline body myopathy. Neurology 62: 1518-1521, 2004. (15136674)
Laing, N. G.; Ceuterick-de Groote, C.; Dye, D. E.; Liyanage, K.; Duff, R. M.; Dubois, B.; Robberecht, W.; Sciot, R.; Martin, J.-J.; Goebel, H. H. : Myosin storage myopathy: slow skeletal myosin (MYH7) mutation in two isolated cases. Neurology 64: 527-529, 2005. (15699387)
MYH7 (14q12)
Myosin, heavy polypeptide 7, cardiac muscle, beta
Myopathy, myosin storage, autosomal recessive - (AR)
3.36
Tajsharghi H, Oldfors A, Macleod D P, Swash M. Homozygous mutation in MYH7 in myosin storage myopathy and cardiomyopathy. Neurology 2007a; 68: 962. (17372140)
MYH7 (14q12)
Myosin, heavy polypeptide 7, cardiac muscle, beta
Myopathy proximal to ophthalmoplegia, recessive (Inclusion body myopathy 3) - (AD/AR)
3.37
Tajsharghi H, Hilton-Jones D, Raheem O, Saukkonen AM, Oldfors A, Udd B. Human disease caused by loss of fast IIa myosin heavy chain due to recessive MYH2 mutations. Brain. 2010 May;133(Pt 5):1451-9. (20418530)
MYH2 (17p13.1)
Myosin, heavy polypeptide 2, skeletal muscle
Isolated inclusion body myopathy - (AD)
3.38
Izumi R., Warita H., Niihori T., et al. Isolated inclusion body myopathy caused by a multisystem proteinopathy-linked hnRNPA1 mutation. Neurol Genet 2015;1:e23. (27066560)
HNRNPA1 (12q13.13)
Heterogeneous nuclear ribonucleoprotein A1
Cap myopathy CAPM1 - (AD, AR)
3.39
De Paula AM, Franques J, Fernandez C, Monnier N, Lunardi J, Pellissier JF, Figarella-Branger D, Pouget J. A TPM3 mutation causing cap myopathy. Neuromuscul Disord. 2009 Oct;19(10):685-8. Epub 2009 Jun 23. (19487656)
Ohlsson M, Fidzianska A, Tajsharghi H, Oldfors A. TPM3 mutation in one of the original cases of cap disease. Neurology. 2009 Jun 2;72(22):1961-3. (19553118)
TPM3 (1q21.2)
Tropomyosin 3
Cap myopathy CAPM2 - (AD)
3.40
Tajsharghi H, Oldfors A, Macleod D P, Swash M. Homozygous mutation in MYH7 in myosin storage myopathy and cardiomyopathy. Neurology 2007a; 68: 962. (17372140)
Lehtokari V L, Ceuterick-de Groote C, de Jonghe P, Marttila M, Laing N G, Pelin K, Wallgren-Pettersson C. Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2. Neuromuscul Disord 2007; 17: 433-42. (17434307)
TPM2 (9p13)
Tropomyosin 2 (beta)
Cap myopathy - (AD)
3.41
Hung RM, Yoon G, Hawkins CE, Halliday W, Biggar D, Vajsar J. Cap myopathy caused by a mutation of the skeletal alpha-actin gene ACTA1. Neuromuscul Disord. 2010 Apr;20(4):238-40. Epub 2010 Mar 19. (20303757)
ACTA1 (1q42.1)
Alpha actin, skeletal muscle
Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) - (AR, AD)
3.42
Sato, I., Wu, S., Ibarra, M. C. A., Hayashi, Y. K., Fujita, H., Tojo, M., Oh, S. J., Nonaka, I., Noguchi, S., Nishino, I. Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation. Neurology 70: 114-122, 2008. (17538032)
RYR1 (19q13.1)
Ryanodine receptor 1 (skeletal)
Salih myopathy, (Congenital myopathy with fatal cardiomyopathy) - (AR)
3.43
Carmignac V, Salih M A, Quijano-Roy S, Marchand S, Al Rayess M M, Mukhtar M M, Urtizberea J A, Labeit S, Guicheney P, Leturcq F, Gautel M, Fardeau M, Campbell K P, Richard I, Estournet B, Ferreiro A. C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy. Ann Neurol 2007; 61: 340-51. (17444505)
TTN (2q31)
Titin
Congenital skeletal myopathy and fatal cardiomyopathy - (AR)
3.44
Tajsharghi H, Leren TP, Abdul-Hussein S, Tulinius M, Brunvand L, Dahl HM, Oldfors A. Unexpected myopathy associated with a mutation in MYBPC3 and misplacement of the cardiac myosin binding protein C. J Med Genet. 2010 Aug;47(8):575-7. Epub 2009 Oct 26. (19858127)
MYBPC3 (11p11.2)
Cardiac myosin binding protein-C
Congenital myopathy Compton-North - (AR)
3.45
Compton AG, Albrecht DE, Seto JT, Cooper ST, Ilkovski B, Jones KJ, Challis D, Mowat D, Ranscht B, Bahlo M, Froehner SC, North KN. Mutations in contactin-1, a neural adhesion and neuromuscular junction protein, cause a familial form of lethal congenital myopathy. Am J Hum Genet. 2008 Dec;83(6):714-24. Epub 2008 Nov 20. (19026398)
CNTN1 (12q11-q12)
Contactin-1
Sarcotubular myopathy - (AR)
3.46
Schoser BG, Frosk P, Engel AG, Klutzny U, Lochm²ºller H, Wrogemann K. 2005. Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H. Ann Neurol 57:591-595. (15786463 )
TRIM32 (9q33.2)
Tripartite motif-containing 32
Congenital myopathy related to HACD1 - (AR)
3.47
Muhammad E, Reish O, Ohno Y, et al. Congenital Myopathy is Caused by Mutation of HACD1. Hum Mol Genet. 2013 Dec 20;22(25):5229-36. doi: 10.1093/hmg/ddt380. Epub 2013 Aug 9. (23933735)
HACD1 (10p12.33)
Protein tyrosine phosphatase-like (3-Hydroxyacyl-CoA dehydratase
Congenital myopathy with ophthalmoplegia related to CACNA1S - (AR)
3.48
Hunter JM, Ahearn ME, Balak CD, Liang WS, Kurdoglu A, Corneveaux JJ, Russell M, Huentelman MJ, Craig DW, Carpten J, Coons SW, DeMello DE, Hall JG, Bernes SM, Baumbach-Reardon L. Mol Genet Genomic Med. 2015 Jul;3(4):283-301. doi: 10.1002/mgg3.142. Epub 2015 Apr 8. (26247046)
CACNA1S (1q32)
Calcium channel, voltage-dependent, L type, alpha 1S subunit
Myopathy, Congenital, With Neuropathy And Deafness - (AR)
3.49
Knierim, E., Gill, E., Seifert, F., Morales-Gonzalez, S., Unudurthi, S. D., Hund, T. J., Stenzel, W., Schuelke, M. A recessive mutation in beta-IV-spectrin (SPTBN4) associates with congenital myopathy, neuropathy, and central deafness. Hum. Genet. 136: 903-910, 2017. (28540413)
SPTBN4 (19q13)
Spectrin, Beta, Nonerythrocytic, 4
Myopathy, congenital, With excess of muscle spindles - (AD)
3.50
Quélin C., Loget P., Rozel C., D’Hervé D., Fradin M., Demurger F., et al. Fetal costello syndrome with neuromuscular spindles excess and p.Gly12Val HRAS mutation. Eur J Med Genet. 2017 Jul;60(7):395-398. (28455154)
HRAS (11p15.5)
V-Ha-RAS Harvey Rat Sarcoma Viral
Carey-Fineman-Ziter syndrome (formerly congenital myopathy with Moebius sequence and Robin sequence) - (AR)
3.51
Di Gioia, S. A., Connors, S., Matsunami, N., Cannavino, J., Rose, M. F., Gilette, N. M., Artoni, P., Sobreira, N. L. M., Chan, W.-M., Webb, B. D., Robson, C. D., Cheng, L., and 24 others. A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome. Nature Commun. 8: 16077, 2017. Note: Electronic Article. (28681861)
MYMK (9q34.2)
Myomaker
Myopathy, congenital, Baily-Bloch (Native American myopathy) - (AR)
3.52
Horstick, E. J., Linsley, J. W., Dowling, J. J., Hauser, M. A., McDonald, K. K., Ashley-Koch, A., Saint-Amant, L., Satish, A., Cui, W. W., Zhou, W., Sprague, S. M., Stamm, D. S., Powell, C. M., Speer, M. C., Franzini-Armstrong, C., Hirata, H., Kuwada, J. Y. Stac3 is a component of the excitation-contraction coupling machinery and mutated in Native American myopathy. Nature Commun. 4: 1952, 2013. (23736855)
STAC3 (12q13.3)
SH3 and cysteine rich domain 3
Myopathy, congenital, with malignant hyperthermia susceptibility - (AR)
3.53
Zaharieva IT, Thor MG, Oates EC, van Karnebeek C, Hendson G, Blom E, Witting N, Rasmussen M, Gabbett MT, Ravenscroft G, Sframeli M, Suetterlin K, Sarkozy A, D'Argenzio L, Hartley L, Matthews E, Pitt M, Vissing J, Ballegaard M, Krarup C, Slørdahl A, Halvorsen H, Ye XC, Zhang LH, Løkken N, Werlauff U, Abdelsayed M, Davis MR, Feng L, Phadke R, Sewry CA, Morgan JE, Laing NG, Vallance H, Ruben P, Hanna MG, Lewis S, Kamsteeg EJ, Männikkö R, Muntoni F. Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy. Brain. 2016 Mar;139(Pt 3):674-91. doi: 10.1093/brain/awv352. Epub 2015 Dec 22. PubMed PMID: 26700687; PubMed Central PMCID: PMC4766374. (26700687)
STAC3 (12q13.3)
SH3 and cysteine rich domain 3
Myopathy congenital with structured cores and Z-line abnormalities - (AD)
3.54
Lornage X, Romero NB, Grosgogeat CA, Malfatti E, Donkervoort S, Marchetti MM, Neuhaus SB, Foley AR, Labasse C, Schneider R, Carlier RY, Chao KR, Medne L, Deleuze JF, Orlikowski D, Bönnemann CG, Gupta VA, Fardeau M, Böhm J, Laporte J. ACTN2 mutations cause "Multiple structured Core Disease" (MsCD). Acta Neuropathol. 2019 Jan 30. doi: 10.1007/s00401-019-01963-8. (30701273)
ACTN2 (1q42-q43)
Actinin alpha2
Myopathy congenital with fast twitch (type II) fiber atrophy - (AR)
3.55
Ravenscroft G, Zaharieva I, Bortolotti CA, Lambrughi M, Pignataro M, Borsari M, Sewry CA, Phadke R, Haliloglu G, Ong R, Goullée H, Whyte T; UK10K Consortium, Manzur A, Talim B, Kaya U, Osborn DP, Forrest A, Laing NG, Muntoni F. Bi-allelic mutations in MYL1 cause a severe congenital myopathy. Hum Mol Genet. 2018 Sep 12. doi: 10.1093/hmg/ddy320. (30215711)
MYL1 (2q34)
Myosin, light polypeptide 1, alkali, skeletal fast
Congenital amyotrophy - (AR)
3.56
Carter MT, McMillan HJ, Tomin A, Weiss N. Compound heterozygous CACNA1H mutations associated with severe congenital amyotrophy. Channels (Austin). 2019 Dec;13(1):153-161. doi: 10.1080/19336950.2019.1614415. (31070086)
CACNA1H (16p13.3)
Calcium channel, voltage-dependent, T type, aplpha-1H subunit
Congenital multi-minicore myopathy - (AR)
3.57
Estan MC, Fernandez-Nunez E, Zaki MS, Esteban MI, Donkervoort S, Hawkins C, Caparros-Martin JA, Saade D, Hu Y, Bolduc V, Chao KR, Nevado J, Lamuedra A, Largo R, Herrero-Beaumont G, Regadera J, Hernandez-Chico C, Tizzano EF, Martinez-Glez V, Carvajal JJ, Zong R, Nelson DL, Otaify GA, Temtamy S, Aglan M, Issa M, Bonnemann CG, Lapunzina P, Yoon G, Ruiz-Perez VL. Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy. Nat Commun. 2019 Feb 15;10(1):797. doi: 10.1038/s41467-019-08548-9. (30770808)
FXR1 (3q26.33)
FMR1 autosomal homolog
Congenital Myopathy related to PAX7 - (AR)
3.58
Feichtinger RG, Mucha BE, Hengel H, Orfi Z, Makowski C, Dort J, D'Anjou G, Nguyen TTM, Buchert R, Juenger H, Freisinger P, Baumeister S, Schoser B, Ahting U, Keimer R, Nguyen CE, Fabre P, Gauthier J, Miguet M, Lopes F, AlHakeem A, AlHashem A, Tabarki B, Kandaswamy KK, Bauer P, Steinbacher P, Prokisch H, Sturm M, Strom TM, Ellezam B, Mayr JA, Schöls L, Michaud JL, Campeau PM, Haack TB, Dumont NA. Biallelic variants in the transcription factor PAX7 are a new genetic cause of myopathy. Genet Med. 2019 May 16. doi: 10.1038/s41436-019-0532-z. [Epub ahead of print] (31092906)
PAX7 (1p36.13)
Paired Box gene 7
Congenital Myopathy related to SCN4A - (AR)
3.59
Zaharieva IT, Thor MG, Oates EC, van Karnebeek C, Hendson G, Blom E, Witting N, Rasmussen M, Gabbett MT, Ravenscroft G, Sframeli M, Suetterlin K, Sarkozy A, D'Argenzio L, Hartley L, Matthews E, Pitt M, Vissing J, Ballegaard M, Krarup C, Slørdahl A, Halvorsen H, Ye XC, Zhang LH, Løkken N, Werlauff U, Abdelsayed M, Davis MR, Feng L, Phadke R, Sewry CA, Morgan JE, Laing NG, Vallance H, Ruben P, Hanna MG, Lewis S, Kamsteeg EJ, Männikkö R, Muntoni F. Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy. Brain. 2016 Mar;139(Pt 3):674-91. doi: 10.1093/brain/awv352. Epub 2015 Dec 22. PubMed PMID: 26700687; PubMed Central PMCID: PMC4766374. (26700687)
Gonorazky HD, Marshall CR, Al-Murshed M, Hazrati LN, Thor MG, Hanna MG, Männikkö R, Ray PN, Yoon G. Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A. Neuromuscul Disord. 2017 Jun;27(6):574-580. doi: 10.1016/j.nmd.2017.02.001. Epub 2017 Feb 8. (28262468)
Sloth CK, Denti F, Schmitt N, Bentzen BH, Fagerberg C, Vissing J, Gaist D. Homozygosity for SCN4A Arg1142Gln causes congenital myopathy with variable disease expression. Neurol Genet. 2018 Sep 19;4(5):e267. doi: 10.1212/NXG.0000000000000267. eCollection 2018 Oct. PubMed PMID: 30283817; PubMed Central PMCID: PMC6167177. (30283817)
SCN4A (17q23-q25.3)
Sodium channel, voltage-gated, type IV, alpha
Congenital Myopathy related to PYROXD1 - (AR)
3.60
Lornage X., Malfatti E., Chéraud C., Schneider R., (28220527)
PYROXD1 (12p12.1)
Pyridine nucleotidedisulphide oxidoreductase domain 1
Congenital Myopathy related to TNPO3 - (AD)
3.61
Vihola A, Palmio J, Danielsson O, Penttilä S, Louiselle D, Pittman S, Weihl C, Udd B. Novel mutation in TNPO3 causes congenital limb-girdle myopathy with slow progression. Neurol Genet. 2019 May 2;5(3):e337. doi: 10.1212/NXG.0000000000000337. eCollection 2019 Jun. PubMed PMID: 31192305; PubMed Central PMCID: PMC6515942. (31192305)
Angelini C, Marozzo R, Pinzan E, Pegoraro V, Molnar MJ, Torella A, Nigro V. A new family with transportinopathy: increased clinical heterogeneity. Ther Adv Neurol Disord. 2019 Jun 9;12:1756286419850433. doi: 10.1177/1756286419850433. eCollection 2019. PubMed PMID: 31217819; PubMed Central PMCID: PMC6558532. (31217819)
TNPO3 (7q32.1-q32.2)
Transportin 3
Scapuloperoneal myopathy, MYH7-related - (AD)
3.62
Pegoraro, E., Gavassini, B. F., Borsato, C., Melacini, P., Vianello, A., Stramere, R., Cenacchi, G., Angelini, C. MYH7 gene mutation in myosin storage myopathy and scapulo-peroneal myopathy. Neuromusc. Disord. 17: 321-329, 2007. (17336526)
MYH7 (14q12)
Myosin, heavy polypeptide 7, cardiac muscle, beta
Congenital myopathy related to UNC45B - (AR)
3.63
Dafsari HS, Kocaturk NM, Daimagüler HS, et al. Bi-allelic mutations in uncoordinated mutant number-45 myosin chaperone B are a cause for congenital myopathy. Acta Neuropathol Commun. 2019;7(1):211. Published 2019 Dec 18. doi:10.1186/s40478-019-0869-1 (31852522)
UNC45B (17q12)
UNC45 Myosin Chaperone B
Dusty core disease related to RYR1 - (AR)
3.64
Garibaldi M, Rendu J, Brocard J, Lacene E, Fauré J, Brochier G, Beuvin M, Labasse C, Madelaine A, Malfatti E, Bevilacqua JA, Lubieniecki F, Monges S, Taratuto AL, Laporte J, Marty I, Antonini G, Romero NB. Dusty core disease' (DuCD): expanding morphological spectrum of RYR1 recessive myopathies. Acta Neuropathol Commun. 2019 Jan 5;7(1):3. doi: 10.1186/s40478-018-0655-5. PMID: 30611313 (30611313)
RYR1 (19q13.1)
Ryanodine receptor 1 (skeletal)