Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene - Sorbonne Université
Journal Articles Journal of Neuromuscular Diseases Year : 2020

Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene

Sergey N Bardakov
  • Function : Author
Roman V Deev
  • Function : Author
Raisat M Magomedova
  • Function : Author
Zoya R Umakhanova
  • Function : Author
Kamil Z Zulfugarov
  • Function : Author
Patimat G Akhmedova
  • Function : Author
Vadim A Tsargush
  • Function : Author
Vadim L Zorin
  • Function : Author
Ekaterina N Chernets
  • Function : Author
Gimat D Dalgatov
  • Function : Author
Fedor A Konovalov
  • Function : Author
Artur A Isaev
  • Function : Author

Abstract

A family of five male siblings (three survivors at 48, 53 and 58 years old; two deceased at 8 months old and 2.5 years old) demonstrating significant phenotypic variability ranging from intermediate to the myosclerotic like Bethlem myopathy is presented. Whole-exome sequencing (WES) identified a new homozygous missense mutation chr21:47402679 T > C in the canonical splice donor site of the second intron (c.227 + 2T>C) in the COL6A1 gene. mRNA analysis confirmed skipping of exon 2 encoding 925 amino-acids in 94-95% of resulting transcripts. Three sibs presented with intermediate phenotype of collagen VI-related dystrophies (48, 53 and 2.5 years old) while the fourth sibling (58 years old) was classified as Bethlem myopathy with spine rigidity. The two older siblings with the moderate progressive phenotype (48 and 53 years old) lost their ability to maintain a vertical posture caused by pronounced contractures of large joints, but continued to ambulated throughout life on fully bent legs without auxiliary means of support. Immunofluorescence analysis of dermal fibroblasts demonstrated that no type VI collagen was secreted in any of the siblings' cells, regardless of clinical manifestations severity while fibroblast proliferation and colony formation ability was decreased. The detailed genetic and long term clinical data contribute to broadening the genotypic and phenotypic spectrum of COL6A1 related disease.
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Dates and versions

hal-03094479 , version 1 (04-01-2021)

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Sergey N Bardakov, Roman V Deev, Raisat M Magomedova, Zoya R Umakhanova, Valérie Allamand, et al.. Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene. Journal of Neuromuscular Diseases, 2020, pp.1-12. ⟨10.3233/JND-200476⟩. ⟨hal-03094479⟩
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