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Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene
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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075389/ https://www.ncbi.nlm.nih.gov/pubmed/33337382 http://dx.doi.org/10.3233/JND-200476 |
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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. |
author_facet | 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. |
author_sort | Bardakov, Sergey N. |
collection | PubMed |
description | 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 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 COL6A1 related disease. |
format | Online Article Text |
id | pubmed-8075389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80753892021-05-11 Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene 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. J Neuromuscul Dis Research Report 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 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 COL6A1 related disease. IOS Press 2021-03-02 /pmc/articles/PMC8075389/ /pubmed/33337382 http://dx.doi.org/10.3233/JND-200476 Text en © 2021 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Report 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. Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene |
title | Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene |
title_full | Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene |
title_fullStr | Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene |
title_full_unstemmed | Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene |
title_short | Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene |
title_sort | intrafamilial phenotypic variability of collagen vi-related myopathy due to a new mutation in the col6a1 gene |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075389/ https://www.ncbi.nlm.nih.gov/pubmed/33337382 http://dx.doi.org/10.3233/JND-200476 |
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