학술논문
Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1Gene
Document Type
Article
Author
Bardakov, Sergey N.; Deev, Roman V.; Magomedova, Raisat M.; Umakhanova, Zoya R.; Allamand, Valérie; Gartioux, Corine; Zulfugarov, Kamil Z.; Akhmedova, Patimat G.; Tsargush, Vadim A.; Titova, Angelina A.; Mavlikeev, Mikhail O.; Zorin, Vadim L.; Chernets, Ekaterina N.; Dalgatov, Gimat D.; Konovalov, Fedor A.; Isaev, Artur A.
Source
Journal of Neuromuscular Diseases; March 2021, Vol. 8 Issue: 2 p273-285, 13p
Subject
Language
ISSN
22143599; 22143602
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 COL6A1gene. 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 ambulate 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 COL6A1related disease.