The UMD-DYSF mutations database
Mutations

All publicly available mutations of the dysferlin gene described or predicted in the literature as deleterious have been uploaded in UMD-DYSF, exclusively.

- List of publications referenced in UMD-DYSF (Show/Hide)

Ref #0. Mutation was not published but patient consented to have his data published on UMD-DYSF

1 - Krahn M et al. Analysis of the DYSF mutational spectrum in a large cohort of patients. Hum Mutat. 2009 Feb;30(2):E345-75 OR Nguyen K et al. Dysferlin mutations in LGMD2B, Miyoshi myopathy, and atypical dysferlinopathies. Hum Mutat. 2005 Aug;26(2):165.

2 - Bashir R et al. A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet. 1998 Sep;20(1):37-42.

3 - Weiler T et al. Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene(s). Hum Mol Genet. 1999 May;8(5):871-7.

4 - Anderson LVet al. Secondary reduction in calpain 3 expression in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy (primary dysferlinopathies). Neuromuscul Disord. 2000 Dec;10(8):553-9.

5 - McNally EM et al. Splicing mutation in dysferlin produces limb-girdle muscular dystrophy with inflammation. Am J Med Genet. 2000 Apr 10;91(4):305-12.

6 - Argov Z et al. Muscular dystrophy due to dysferlin deficiency in Libyan Jews. Clinical and genetic features. Brain. 2000 Jun;123 ( Pt 6):1229-37.

7 - Mahjneh I et al. Dysferlinopathy (LGMD2B): a 23-year follow-up study of 10 patients homozygous for the same frameshifting dysferlin mutations. Neuromuscul Disord. 2001 Jan;11(1):20-6.

8 - Liu J et al. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet. 1998 Sep;20(1):31-6.

9 - Illa I et al. Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype. Ann Neurol. 2001 Jan;49(1):130-4.

10 - Matsuda C et al. The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle. Hum Mol Genet. 2001 Aug 15;10(17):1761-6.

11 - Aoki M et al. Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy. Neurology. 2001 Jul 24;57(2):271-8.

12 - Saito A et al. Miyoshi myopathy patients with novel 5' splicing donor site mutations showed different dysferlin immunostaining at the sarcolemma. Acta Neuropathol. 2002 Dec;104(6):615-20.

13 - Takahashi T et al. Dysferlin mutations in Japanese Miyoshi myopathy: relationship to phenotype. Neurology. 2003 Jun 10;60(11):1799-804.

14 - Nagashima T et al. Dysferlinopathy associated with rigid spine syndrome. Neuropathology. 2004 Dec;24(4):341-6.

15 - Suzuki N et al. Novel dysferlin mutations and characteristic muscle atrophy in late-onset Miyoshi myopathy. Muscle Nerve. 2004 May;29(5):721-3.

16 - Cagliani R et al. Molecular analysis of LGMD-2B and MM patients: identification of novel DYSF mutations and possible founder effect in the Italian population. Neuromuscul Disord. 2003 Dec;13(10):788-95.

17 - Cagliani Ret al. Mutation finding in patients with dysferlin deficiency and role of the dysferlin interacting proteins annexin A1 and A2 in muscular dystrophies. Hum Mutat. 2005 Sep;26(3):283.

18 - Nakagawa M et al. Phenotypic variation in a large Japanese family with Miyoshi myopathy with nonsense mutation in exon 19 of dysferlin gene. J Neurol Sci. 2001 Feb 15;184(1):15-9.

19 - Tagawa K et al. Protein and gene analyses of dysferlinopathy in a large group of Japanese muscular dystrophy patients. J Neurol Sci. 2003 Jul 15;211(1-2):23-8.

20 - Illarioshkin SN et al. Identical dysferlin mutation in limb-girdle muscular dystrophy type 2B and distal myopathy. Neurology. 2000 Dec 26;55(12):1931-3.

21 - Ueyama H et al. A new dysferlin gene mutation in two Japanese families with limb-girdle muscular dystrophy 2B and Miyoshi myopathy. Neuromuscul Disord. 2001 Mar;11(2):139-45.

22 - Walter MC et al. Variable reduction of caveolin-3 in patients with LGMD2B/MM. J Neurol. 2003 Dec;250(12):1431-8.

23 - Kawabe K et al. Dysferlin mutation analysis in a group of Italian patients with limb-girdle muscular dystrophy and Miyoshi myopathy. Eur J Neurol. 2004 Oct;11(10):657-61.

24 - Oh SH et al. Identification of a dysferlin gene mutation in a Korean case with Miyoshi myopathy. Yonsei Med J. 2004 Oct 31;45(5):927-30.

25 - Shunchang S et al. Dysferlin mutation in a Chinese pedigree with Miyoshi myopathy. Clin Neurol Neurosurg. 2006 Jun;108(4):369-73. Epub 2005 Jul 14.

26 - Ro LS et al. Phenotypic features and genetic findings in 2 chinese families with Miyoshi distal myopathy. Arch Neurol. 2004 Oct;61(10):1594-9.

27. Vilchez JJ et al. Identification of a novel founder mutation in the DYSF gene causing clinical variability in the Spanish population. Arch Neurol. 2005 Aug;62(8):1256-9.

28. Brummer D et al. Long-term MRI and clinical follow-up of symptomatic and presymptomatic carriers of dysferlin gene mutations. Acta Myol. 2005 Jul;24(1):6-16.

29. Sinnreich M et al. Lariat branch point mutation in the dysferlin gene with mild limb-girdle muscular dystrophy. Neurology. 2006 Apr 11;66(7):1114-6.

30. Wenzel K et al. Novel sequence variants in dysferlin-deficient muscular dystrophy leading to mRNA decay and possible C2-domain misfolding. Hum Mutat. 2006 Jun;27(6):599-600.

31. Takahashi T et al. A case of dysferlinopathy presenting choreic movements. Mov Disord. 2006 Sep;21(9):1513-5.

32. Cho HJ et al. Clinical and genetic analysis of Korean patients with Miyoshi myopathy: identification of three novel mutations in the DYSF gene. J Korean Med Sci. 2006 Aug;21(4):724-7.

33. Fanin M et al. Muscle protein analysis in the detection of heterozygotes for recessive limb girdle muscular dystrophy type 2B and 2E. Neuromuscul Disord. 2006 Nov;16(11):792-9.

34. Therrien C et al. Mutation impact on dysferlin inferred from database analysis and computer-based structural predictions. J Neurol Sci. 2006 Dec 1;250(1-2):71-8.

35. De Luna N et al. Dysferlin expression in monocytes: a source of mRNA for mutation analysis. Neuromuscul Disord. 2007 Jan;17(1):69-76.

36. Diers A et al. Painful enlargement of the calf muscles in limb girdle muscular dystrophy type 2B (LGMD2B) with a novel compound heterozygous mutation in DYSF. Neuromuscul Disord. 2007 Feb;17(2):157-62.

37. Illa I et al. Symptomatic dysferlin gene mutation carriers: characterization of two cases. Neurology. 2007 Apr 17;68(16):1284-9.

38. Hattori H et al. A novel compound heterozygous dysferlin mutation in Miyoshi myopathy siblings responding to dantrolene. Eur J Neurol. 2007 Nov;14(11):1288-91.

39. Leshinsky-Silver E et al. Dysferlinopathy in the Jews of the Caucasus: a frequent mutation in the dysferlin gene. Neuromuscul Disord. 2007 Dec;17(11-12):950-4.

40. Lo HP et al. Limb-girdle muscular dystrophy: diagnostic evaluation, frequency and clues to pathogenesis. Neuromuscul Disord. 2008 Jan;18(1):34-44.

41. Saito H et al. Distal anterior compartment myopathy with early ankle contractures. Muscle Nerve. 2007 Oct;36(4):525-7.

42. van der Kooi AJ et al. Limb-girdle muscular dystrophy in the Netherlands: gene defect identified in half the families. Neurology. 2007 Jun 12;68(24):2125-8.

43. Wenzel K et al. Dysfunction of dysferlin-deficient hearts. J Mol Med. 2007 Nov;85(11):1203-14.

44. Guglieri M et al. Clinical, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients. Hum Mutat. 2008 Feb;29(2):258-66.

45. Spuler S et al. Dysferlin-deficient muscular dystrophy features amyloidosis. Ann Neurol. 2008 Mar;63(3):323-8.

46. Nagaraju K et al. Dysferlin deficiency enhances monocyte phagocytosis: a model for the inflammatory onset of limb-girdle muscular dystrophy 2B. Am J Pathol. 2008 Mar;172(3):774-85.

47. Rosas-Vargas H et al. Dysferlin homozygous mutation G1418D causes limb-girdle type 2B in a Mexican family. Genet Test. 2007 Winter;11(4):391-6.

48. Klinge L et al. Late onset in dysferlinopathy widens the clinical spectrum. Neuromuscul Disord. 2008 Apr;18(4):288-90.

49. Gal A et al. Challenges for the genetic screening in dysferlin deficiency--report of an instructive case and review of the literature. Clin Neuropathol. 2008 Sep-Oct;27(5):289-94.

50. Kesari A et al. Dysferlin deficiency shows compensatory induction of Rab27A/Slp2a that may contribute to inflammatory onset. Am J Pathol. 2008 Nov;173(5):1476-87.

51. Khadilkar SV et al. Twenty-two year follow-up of an Indian family with dysferlinopathy-clinical, immunocytochemical, western blotting and genetic features. Neurol India. 2008 Jul-Sep;56(3):388-90.

52. Paradas C et al. A new phenotype of dysferlinopathy with congenital onset. Neuromuscul Disord. 2009 Jan;19(1):21-5.

53. Liewluck T et al. Novel DYSF mutations in Thai patients with distal myopathy. Clin Neurol Neurosurg. 2009 Sep;111(7):613-8.

54. Klinge L et al. New aspects on patients affected by dysferlin deficient muscular dystrophy. J Neurol Neurosurg Psychiatry. 2010 Sept;81(9):946-53.

55. Krahn M et al. Identification of different genomic deletions and one duplication in the dysferlin gene using multiplex ligation-dependent probe amplification and genomic quantitative PCR. Genet Test Mol Biomarkers. 2009 Aug;13(4):439-42.

56. Vinit J et al. Dysferlin deficiency treated like refractory polymyositis. Clin Rheumatol. 2010 Jan;29(1):103-6.

57. Seror P et al. Complete fatty degeneration of lumbar erector spinae muscles caused by a primary dysferlinopathy. Muscle Nerve. 2008 Mar;37(3):410-4.

58. Rosales XQ et al. Novel diagnostic features of dysferlinopathies. Muscle Nerve. 2010 Jul;42(1):14-21.

59. Santos R et al. Private dysferlin exon skipping mutation (c.5492G>A) with a founder effect reveals further alternative splicing involving exons 49-51. J Hum Genet. 2010 Aug;55(8):546-9.

60. Krahn M et al. A naturally occurring human minidysferlin protein repairs sarcolemmal lesions in a mouse model of dysferlinopathy. Sci Transl Med. 2010 Sep 22;2(50):50ra69.

61. Hayashi S et al. Rapid screening for Japanese dysferlinopathy by fluorescent primer extension. Intern Med. 2010;49(24):2693-6.

62. Vernengo L et al. Novel ancestral Dysferlin splicing mutation which migrated from the Iberian peninsula to South America. Neuromuscul Disord. 2011 May;21(5):328-37.

63. Walsh R et al. Progressive dysphagia in limb-girdle muscular dystrophy type 2B. Muscle Nerve. 2011 May;43(5):761-4.

64. Cacciottolo M et al. Muscular dystrophy with marked Dysferlin deficiency is consistently caused by primary dysferlin gene mutations. Eur J Hum Genet. 2011 Sep;19(9):974-80.

65. Meznaric M et al. Abnormal expression of dysferlin in skeletal muscle and monocytes supports primary dysferlinopathy in patients with one mutated allele. Eur J Neurol. 2011 Jul;18(7):1021-3.

66. Rosales XQ et al. Cardiovascular magnetic resonance of cardiomyopathy in limb girdle muscular dystrophy 2B and 2I. J Cardiovasc Magn Reson. 2011 Aug 4;13:39.

67. Gallardo E et al. Comparison of dysferlin expression in human skeletal muscle with that in monocytes for the diagnosis of dysferlin myopathy. PLoS One. 2011;6(12):e29061.

68. Park YE et al. Two common mutations (p.Gln832X and c.663+1G>C) account for about a third of the DYSF mutations in Korean patients with dysferlinopathy. Neuromuscul Disord. 2012 Jan 30.

69. Takahashi T et al. Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B. J Neurol Neurosurg Psychiatry. 2013 Apr;84(4):433-40.

70. Zhao Z et al. DYSF mutation analysis in a group of Chinese patients with dysferlinopathy. Clin Neurol Neurosurg. 2012 Dec 14.

71. Nilsson MI et al. Dysferlin aggregation in limb-girdle muscular dystrophy type 2B/myoshi myopathy necessitates mutational screen for diagnosis. Muscle Nerve. 2013 May;47(5):740-7.

72. Xi J et al. Clinical heterogeneity and a high proportion of novel mutations in a Chinese cohort of patients with dysferlinopathy. Neurol India. 2014 Nov-Dec;62(6):635-9.

73. Jethwa H et al. Limb girdle muscular dystrophy type 2B masquerading as inflammatory myopathy: case report. Pediatr Rheumatol Online J. 2013 May 3;11(1):19.

74. Linssen WH et al. Long-term follow-up study on patients with Miyoshi phenotype of distal muscular dystrophy. Eur J Neurol. 2013 Jun;20(6):968-74.

75. Ankala A et al. Diagnostic overview of blood-based dysferlin protein assay for dysferlinopathies. Muscle Nerve. 2014 Feb 1.

76. Szymanska S et al. Case report of an adolescent girl with limb-girdle muscular dystrophy type 2B - the usefulness of muscle protein immunostaining in the diagnosis of dysferlinopathies. Folia Neuropathol. 2014;52(4):452-6.

77. Dominov JA et al. A novel dysferlin mutant pseudoexon bypassed with antisense oligonucleotides. Ann Clin Transl Neurol. 2014 Sep;1(9):703-20.

78. Bartoli M et al. Exome sequencing as a second-tier diagnostic approach for clinically suspected dysferlinopathy patients. Muscle Nerve. 2014 Dec;50(6):1007-10.

79. Ceyhan-Birsoy O et al. Whole Exome Sequencing Reveals DYSF, FKTN, and ISPD Mutations in Congenital Muscular Dystrophy Without Brain or Eye Involvement. J Neuromuscul Dis. 2015;2(1):87-92.

80. Liu F et al. Dysferlinopathy: Mitochondrial Abnormalities in Human Skeletal Muscle. Int J Neurosci. 2015 May 22:1-22. [Epub ahead of print]

81. Kergourlay V et al. Comment on: A novel dysferlin-mutant pseudoexon bypassed with antisense oligonucleotides. Annals of Clinical and Translational Neurology. [Epub ahead of print]

UMD-DYSF v1.4 currently contains 1174 entries, each entry corresponding to one mutation associated with one affected individual, either index patient or affected relative. UMD-DYSF entries include 416 different disease-causing mutations identified in 843 patients worldwide. Mutations with no clear pathogenic effect were not collected in UMD-DYSF. A list of known polymorphisms of the dysferlin gene is available on the Leiden Muscular Dystrophy pages and on the UCSC Genome Browser pages. The DYSF gene has a large mutational spectrum with a high proportion of missense changes or frameshifting insertions and/or deletions. Among DYSF disease-causing mutations, a total of seven founder mutations have been reported. Analysis of the distribution of mutations along the CDS and domains shows no mutational hotspot.

UMD-DYSF v1.4 data (June 16, 2015) in a tab-delimited file for download

UMD-DYSF v1.3 data (March 16, 2015) in a tab-delimited file for download

UMD-DYSF v1.2 data (July 8, 2014) in a tab-delimited file for download

UMD-DYSF v1.1 data (April 26, 2013) in a tab-delimited file for download

UMD-DYSF v1.0 data (April 12, 2011) in a tab-delimited file for download

- Table of founder mutations (Show/Hide)

- Table of recurrent mutations in the dysferlin gene

Mutation names in UMD-DYSF are given according to nomenclature guidelines from the Human Genome Variation Society (den Dunnen and Antonarakis 2003, http://www.hgvs.org/mutnonem/) and numbered with respect to the DYSF gene cDNA sequence (+1=A of ATG) (NM_003494.2, Homo sapiens dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) (DYSF), mRNA). An anonymous ID is attributed to each patient data included in the database (Sample ID, for example AUS19-1-1-0).

Different tools are available to search for mutations in UMD-DYSF or to analyze novel mutations not referenced in the database:

* I Found a Mutation
Determines the frequency of a given mutation in the database. Displays a table of the various mutational events for this position. If your mutation is not listed in this database, you can check if it is reported as a known polymorphism on the Leiden Muscular Dystrophy pages.

* I Want to Analyze the Impact of a Missense Variant
This feature uses the UMD-Predictor® algorithm (Frederic et al. 2009) to predict the pathogenicity of all possible non-synonymous or synonymous mutations from the DYSF gene.

* I Want to Analyze an Intronic Variant
The Human Splicing Finder tool (Desmet et al. 2009) evaluates the consequences of substitutions on splicing.

* I Want to Search the Database
Allows the selection of a specific subset of the database. Results are displayed as a list on the screen along with a request ID corresponding to the search. A previous set of records can be displayed entering its corresponding request ID. The user can also customize the display format.

If you want to submit a mutation, please contact M. Krahn.

Mutationn	Geographic/ethnic origin	Evaluated carrier frequency	Reference
c.1180_1180+7delAGTGCGTG (r.1054_1284del, p.Glu353_Leu429del)	Portuguese population	Unknown	#62: Vernengo et al., 2011
c.2372C>G (p.Pro791Arg)	Native canadian population	Unknown	#3: Weiler et al., 1999
c.2779delG (p.Ala927LeufsX21)	Caucasian jewish population	4%	#39: Leshinsky-Silver et al., 2007
c.2875C>T (p.Arg959Trp)	Italian population	Unknown	#16: Cagliani et al., 2003
c.4872_4876delinsCCCC (p.Glu1624AspfsX9)	Libanese jewish population	10%	#6: Argov et al., 2000
c.5492G>A (exon skipping)	Portuguese population	Unknown	#59 Santos et al. 2010
c.5713C>T (p.Arg1905X)	Spanish population(region of Sueca)	2%	#27: Vilchez et al., 2005

The UMD-DYSF mutations database Mutations

The UMD-DYSF mutations database
Mutations