Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2021
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
_version_ 1783684531554877440
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
work_keys_str_mv AT bardakovsergeyn intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT deevromanv intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT magomedovaraisatm intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT umakhanovazoyar intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT allamandvalerie intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT gartiouxcorine intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT zulfugarovkamilz intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT akhmedovapatimatg intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT tsargushvadima intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT titovaangelinaa intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT mavlikeevmikhailo intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT zorinvadiml intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT chernetsekaterinan intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT dalgatovgimatd intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT konovalovfedora intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene
AT isaevartura intrafamilialphenotypicvariabilityofcollagenvirelatedmyopathyduetoanewmutationinthecol6a1gene