4. DISTAL MYOPATHIES (Return to Disease group)
Disease phenotype
Item in this table
References
Gene symbol (chromosome)
protein
Miyoshi muscular dystrophy 1 - (AR)
4.1
Bejaoui K, Hirabayashi K, Hentati F, Haines JL, Ben Hamida C, Belal S, Miller RG, McKenna-Yasek D, Weissenbach J, Rowland LP, et al. Linkage of Miyoshi myopathy (distal autosomal recessive muscular dystrophy) locus to chromosome 2p12-14. Neurology. 1995 Apr;45(4):768-72. (7723968)
Liu J, Aoki M, Illa I, Wu C, Fardeau M, Angelini C, Serrano C, Urtizberea JA, Hentati F, Hamida MB, Bohlega S, Culper EJ, Amato AA, Bossie K, Oeltjen J, Bejaoui K, McKenna-Yasek D, Hosler BA, Schurr E, Arahata K, de Jong PJ, Brown RH Jr. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet. 1998 Sep;20(1):31-6. (9731526)
DYSF (2p12-14)
Dysferlin
Tibial muscular dystrophy (Udd myopathy) - (AD)
4.2
Haravuori H, Vihola A, Straub V, Auranen M, Richard I, Marchand S, Voit T, Labeit S, Somer H, Peltonen L, Beckmann JS, Udd B. Secondary calpain3 deficiency in 2q-linked muscular dystrophy: titin is the candidate gene. Neurology. 2001 Apr 10;56(7):869-77. (9497249)
Hackman, P.; Vihola, A.; Haravuori, H.; Marchand, S.; Sarparanta, J.; de Seze, J.; Labeit, S.; Witt, C.; Peltonen, L.; Richard, I.; Udd, B. : Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. Am. J. Hum. Genet. 71: 492-500, 2002. (12145747)
Haravuori H, Makela-Bengs P, Udd B, Partanen J, Pulkkinen L, Somer H, Peltonen L. Assignment of the tibial muscular dystrophy locus to chromosome 2q31. Am J Hum Genet. 1998 Mar;62(3):620-6. Neuromuscul Disord. 2004 Mar;14(3):183-7 (11294923)
TTN (2q31)
Titin
Nonaka Myopathy - (AR)
4.3
Mitrani-Rosenbaum S, Argov Z, Blumenfeld A, Seidman CE, Seidman JG. Hereditary inclusion body myopathy maps to chromosome 9p1-q1. Hum Mol Genet. 1996 Jan;5(1):159-163. (11528398)
Ikeuchi T, Asaka T, Saito M, Tanaka H, Higuchi S, Tanaka K, Saida K, Uyama E, Mizusawa H, Fukuhara N, Nonaka I, Takamori M, Tsuji S. Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome 9. Ann Neurol. 1997 Apr;41(4):432-7. (8789455)
Eisenberg I, Avidan N, Potikha T, Hochner H, Chen M, Olender T, Barash M, Shemesh M, Sadeh M, Grabov-Nardini G, Shmilevich I, Friedmann A, Karpati G, Bradley WG, Baumbach L, Lancet D, Asher EB, Beckmann JS, Argov Z, Mitrani-Rosenbaum S. The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy. Nat Genet. 2001 Sep;29(1):83-7. (9124799)
GNE (9p13.3)
UDP-N-acetylglucosamine-2- epimerase/N-acetylmannosamine kinase
Distal myopathy 1 (Laing) - (AD)
4.4
Laing NG, Laing BA, Meredith C, et al. Autosomal dominant distal myopathy: linkage to chromosome 14. Am J Hum Genet 1995;56:422-427. (12062252)
Mastaglia, F. L.; Phillips, B. A.; Cala, L. A.; Meredith, C.; Egli, S.; Akkari, P. A.; Laing, N. G. : Early onset chromosome 14-linked distal myopathy (Laing). Neuromusc. Disord. 12: 350-357, 2002. (15322983)
Meredith C, Herrmann R, Parry C, Liyanage K, Dye DE, Durling HJ, Duff RM, Beckman K, de Visser M, van der Graaff MM, Hedera P, Fink JK, Petty EM, Lamont P, Fabian V, Bridges L, Voit T, Mastaglia FL, Laing NG. Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1). Am J Hum Genet. 2004 Oct;75(4):703-8. Epub 2004 Aug 20. (7847377)
MYH7 (14q12)
Myosin, heavy polypeptide 7, cardiac muscle, beta
Vocal cord and pharyngeal distal myopathy (VCPDM) reclassfied as ALS21 - (AD)
4.5
Feit, H.; Silbergleit, A.; Schneider, L. B.; Gutierrez, J. A.; Fitoussi, R.-P.; Reyes, C.; Rouleau, G. A.; Brais, B.; Jackson, C. E.; Beckmann, J. S.; Seboun, E. : Vocal cord and pharyngeal weakness with autosomal dominant distal myopathy: clinical description and gene localization to 5q31. Am. J. Hum. Genet. 63: 1732-1742, 1998. (9837826)
MATR3 (5q31)
Matrin 3
Myopathy distal 3 - (AD)
4.6
Haravuori H, Siitonen HA, Mahjneh I, Hackman P, Lahti L, Somer H, Peltonen L, Kestila M, Udd B. Linkage to two separate loci in a family with a novel distal myopathy phenotype (MPD3). Neuromuscul Disord. 2004 Mar;14(3):183-7. (15036327)
? - (8p22-q11)
Welander distal myopathy - (AD)
4.7
Ahlberg, G.; von Tell, D.; Borg, K.; Edstrom, L.; Anvret, M. : Genetic linkage of Welander distal myopathy to chromosome 2p13. Ann. Neurol. 46: 399-404, 1999. (23401021)
Klar, J., Sobol, M., Melberg, A., Mabert, K., Ameur, A., Johansson, A. C. V., Feuk, L., Entesarian, M., Orlen, H., Casar-Borota, O., Dahl, N. Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing. Hum. Mutat. 34: 572-577, 2013. (10482271)
Hackman, P., Sarparanta, J., Lehtinen, S., Vihola, A., Evila, A., Jonson, P. H., Luque, H., Kere, J., Screen, M., Chinnery, P. F., Ahlberg, G., Edstrom, L., Udd, B. Welander distal myopathy is caused by a mutation in the RNA-binding protein TIA1. Ann. Neurol. 73: 500-509, 2013. (23348830)
TIA1 (2p13)
Cytotoxic granuleassociated RNA binding protein
Welander-like distal myopathy - (Digenic)
4.8
Lee Y, Jonson PH, Sarparanta J, et al. TIA1 variant drives myodegeneration in multisystem proteinopathy with SQSTM1 mutations. J Clin Invest. 2018;128(3):1164-1177. doi:10.1172/JCI97103 (29457785)
SQSTM1 (5q35.3)
Sequestosome 1
TIA1 (2p13)
Cytotoxic granuleassociated RNA binding protein
Vacuolar neuromyopathy - (AD)
4.9
Servidei S, et al. (1999). A distinctive autosomal dominant vacuolar neuromyopathy linked to 19p13. Neurology 53:830-837. (10489050)
? - (19p13)
Distal myopathy with myotilin defect - (AD)
4.10
P²©nisson-Besnier I, et al. (1998). Autosomal dominant late adult onset distal leg myopathy. Neuromsuc Disord 8:459-466. (16793270)
P²©nisson-Besnier I, Talvinen K, Dumez C, Vihola A, Dubas F, Fardeau M, Hackman P, Carpen O and Udd B. Myotilinopathy in a late onset myopathy family. Neuromusc Disord 2006; 16:427-31. (9829275)
MYOT (5q31)
Myotilin
Distal myopathy with nebulin defect - (AR)
4.11
Wallgren-Pettersson C, Lehtokari V L, Kalimo H, Paetau A, Nuutinen E, Hackman P, Sewry C, Pelin K, Udd B. Distal myopathy caused by homozygous missense mutations in the nebulin gene. Brain 2007; 130: 1465-76. (17525139)
NEB (2q22)
Nebulin
Distal myopathy with nebulin defect - (AD)
4.12
Kiiski KJ, Lehtokari VL, Vihola AK, et al. Dominantly inherited distal nemaline/cap myopathy caused by a large deletion in the nebulin gene. Neuromuscul Disord. 2019;29(2):97-107. doi:10.1016/j.nmd.2018.12.007 (30679003)
NEB (2q22)
Nebulin
Distal myopathy with caveolin defect - (AD)
4.13
Tateyama M, Aoki M, Nishino I, Hayashi YK, Sekiguchi S, Shiga Y, Takahashi T, Onodera Y, Haginoya K, Kobayashi K, Iinuma K, Nonaka I, Arahata K and Itoyama Y. Mutation in the caveolin-3 gene causes a peculiar form of distal myopathy. Neurology 2002;58:323-5. (15580566)
Fulizio, L.; Nascimbeni, A. C.; Fanin, M.; Piluso, G.; Politano, L.; Nigro, V.; Angelini, C. : Molecular and muscle pathology in a series of caveolinopathy patients. Hum. Mutat. 25: 82-89, 2005. (11805270)
CAV3 (3p25.3)
Caveolin 3
Late onset distal myopathy (Markesbery-Griggs) - (AD)
4.14
Griggs R, Vihola A, Hackman P, Talvinen K, Haravuori H, Faulkner G, Eymard B, Richard I, Selcen D, Engel A, Carpen O, Udd B. Zaspopathy in a large classic late-onset distal myopathy family. Brain 2007; 130: 1477-84. (17337483)
LDB3 (10q22)
LIM domain binding 3
Miyoshi muscular dystrophy 3 - (AR)
4.15
Bolduc V, Marlow G, Boycott KM, Saleki K, Inoue H, Kroon J, Itakura M, Robitaille Y, Parent L, Baas F, Mizuta K, Kamata N, Richard I, Linssen WH, Mahjneh I, de Visser M, Bashir R, Brais B. Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. Am J Hum Genet. 2010 Feb 12;86(2):213-21. Epub 2010 Jan 21. (20096397)
ANO5 (11p14-12)
Anoctamin 5
Distal myopathy related to DNM2 - (AD)
4.16
Fischer D, Herasse M, Bitoun M, Barrag²°n-Campos HM, Chiras J, Lafor²™t P, Fardeau M, Eymard B, Guicheney P, Romero NB. Characterization of the muscle involvement in dynamin 2-related centronuclear myopathy. Brain. 2006 Jun;129(Pt 6):1463-9. Epub 2006 Apr 3. (16585051)
DNM2 (19p13.2)
Dynamin 2
Early onset distal myopathy with KLHL9 mutations - (AD)
4.17
Cirak S, von Deimling F, Sachdev S, Errington WJ, Herrmann R, B²∂nnemann C, Brockmann K, Hinderlich S, Lindner TH, Steinbrecher A, Hoffmann K, Priv²© GG, Hannink M, N²ºrnberg P, Voit T. Kelch-like homologue 9 mutation is associated with an early onset autosomal dominant distal myopathy. Brain. 2010 Jul;133(Pt 7):2123-35. Epub 2010 Jun 16. (20554658)
KLHL9 (9p21.2-p22.3)
Kelch-like homologue 9
Distal Myopathy 4 - (AD)
4.18
Duff RM, Tay V, Hackman P, Ravenscroft G, McLean C, Kennedy P, Steinbach A, Schöffler W, van der Ven PF, Fürst DO, Song J, Djinovi?-Carugo K, Penttilä S, Raheem O, Reardon K, Malandrini A, Gambelli S, Villanova M, Nowak KJ, Williams DR, Landers JE, Brown RH Jr, Udd B, Laing NG. Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy. Am J Hum Genet. 2011 Jun 10;88(6):729-40. Epub 2011 May 27. (21620354)
FLNC (7q32)
Filamin C, gamma (actin-binding protein - 280)
Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1 - (AD)
4.19
Palmio J, Sandell S, Suominen T, Penttilä S, Raheem O, Hackman P, Huovinen S, Haapasalo H, Udd B. Distinct distal myopathy phenotype caused by VCP gene mutation in a Finnish family. Neuromuscul Disord. 2011 Aug;21(8):551-5. doi: 10.1016/j.nmd.2011.05.008. (21684747)
VCP (9p13-p12)
Valosin-containing protein
Distal myopathy 5 - (AR)
4.20
Park, H. J., Hong, Y. B., Choi, Y.-C., Lee, J., Kim, E. J., Lee, J.-S., Mo, W. M., Ki, S. M., Kim, H. I., Kim, H. J., Hyun, Y. S., Hong, H. D., and 11 others. ADSSL1 mutation relevant to autosomal recessive adolescent onset distal myopathy. Ann. Neurol. 79: 231-243, 2016. (26506222)
ADSSL1 (14q32-33)
Adénylosuccinate synthase-like
Myopathy, distal, with rimmed vacuoles - (AD)
4.21
Bucelli, R. C., Arhzaouy, K., Pestronk, A., Pittman, S. K., Rojas, L., Sue, C. M., Evila, A., Hackman, P., Udd, B., Harms, M. B., Weihl, C. C. SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles. Neurology 85: 665-674, 2015. (26208961)
SQSTM1 (5q35.3)
Sequestosome 1
Myopathy, distal, with rimmed vacuoles - (AD)
4.22
Ruggieri, A., Brancati, F., Zanotti, S., Maggi, L., Pasanisi, M. B., Saredi, S., Terracciano, C., Antozzi, C., D'Alpice, M. R., Sangiuolo, F., Novelli, G., Marshall, C. R., Scherer, S. W., Morandi, L., Federici, L., Massa, R., Mora, M., Minassian, B. A. Complete loss of the DNAJB6 G/F domain and novel missense mutations cause distal-onset DNAJB6 myopathy. Acta Neuropath. Commun. 3: 44, 2015. Note: Electronic Article. (26205529)
DNAJB6 (7q36)
HSP-40 homologue, subfamily B, number 6
Distal myopathy - (AD)
4.23
Palmio J, Jonson PH, Inoue M, et al. Mutations in the J domain of DNAJB6 cause dominant distal myopathy. Neuromuscul Disord. 2020;30(1):38-46. doi:10.1016/j.nmd.2019.11.005 (31955980)
DNAJB6 (7q36)
HSP-40 homologue, subfamily B, number 6
Rimmed vacuole myopathy - (AD)
4.24
Al-Tahan S, Weiss L, Yu H, Tang S, Saporta M, Vihola A, Mozaffar T, Udd B, Kimonis V. New family with HSPB8-associated autosomal dominant rimmed vacuolar myopathy. Neurol Genet. 2019 Jul 10;5(4):e349. doi: 10.1212/NXG.0000000000000349. eCollection 2019 Aug. (31403083)
HSPB8 (12q24.23)
Heat shock 27kDa protein 8
Distal Myopathy 6, Adult-onset - (AR)
4.25
Savarese, M., Palmio, J., Poza, J. J., Weinberg, J., Olive, M., Cobo, A. M., Vihola, A., Jonson, P. H., Sarparanta, J., Garcia-Bragado, F., Urtizberea, J. A., Hackman, P., Udd, B. Actininopathy: a new muscular dystrophy caused by ACTN2 dominant mutations. Ann. Neurol. 85: 899-906, 2019. (30900782)
ACTN2 (1q42-q43)
Actinin alpha2
Distal Myopathy and motor neuropathy - (AD)
4.26
Ghaoui R, Palmio J, Brewer J, et al. Mutations in HSPB8 causing a new phenotype of distal myopathy and motor neuropathy [published correction appears in Neurology. 2016 Mar 15;86(11):1077]. Neurology. 2016;86(4):391-398. doi:10.1212/WNL.0000000000002324 (26718575)
HSPB8 (12q24.23)
Heat shock 27kDa protein 8
Distal Myopathy with protein inclusions - (XLD)
4.27
Johari M, Sarparanta J, Vihola A, Jonson PH, Savarese M, Jokela M, Torella A, Piluso G, Said E, Vella N, Cauchi M, Magot A, Magri F, Mauri E, Kornblum C, Reimann J, Stojkovic T, Romero NB, Luque H, Huovinen S, Lahermo P, Donner K, Comi GP, Nigro V, Hackman P, Udd B. Missense mutations in small muscle protein X-linked (SMPX) cause distal myopathy with protein inclusions. Acta Neuropathol. 2021 Aug;142(2):375-393. doi: 10.1007/s00401-021-02319-x. Epub 2021 May 11. PMID: 33974137; PMCID: PMC8270885. (33974137)
SMPX (Xp22.12)
Small Muscle Protein, X-linked
Distal Myopathy - (AD)
4.28
Ruggieri A, Naumenko S, Smith MA, Iannibelli E, Blasevich F, Bragato C, Gibertini S, Barton K, Vorgerd M, Marcus K, Wang P, Maggi L, Mantegazza R, Dowling JJ, Kley RA, Mora M, Minassian BA. Multiomic elucidation of a coding 99-mer repeat-expansion skeletal muscle disease. Acta Neuropathol. 2020 Aug;140(2):231-235. doi: 10.1007/s00401-020-02164-4. Epub 2020 May 25. PMID: 32451610; PMCID: PMC7360652. (32451610)
PLIN4 (19p13.3)
Perilipin 4