Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene
| العنوان: | Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene |
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| المؤلفون: | Vadim A. Tsargush, Roman V. Deev, Angelina Titova, V.L. Zorin, Patimat G. Akhmedova, Isaev Artur Aleksandrovich, M O Mavlikeev, C. Gartioux, Sergey N. Bardakov, Raisat M. Magomedova, Fedor A. Konovalov, Valérie Allamand, Zoya R. Umakhanova, Ekaterina N. Chernets, Gimat D. Dalgatov, Kamil Z. Zulfugarov |
| المساهمون: | Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Kazan Federal University (KFU), Centre de recherche en Myologie – U974 SU-INSERM |
| المصدر: | Journal of Neuromuscular Diseases Journal of Neuromuscular Diseases, IOS Press, 2020, pp.1-12. ⟨10.3233/JND-200476⟩ |
| بيانات النشر: | IOS Press, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Research Report, Male, medicine.medical_specialty, Contracture, Genotype, Ullrich congenital muscular dystrophy, [SDV]Life Sciences [q-bio], COL6A1, Mutation, Missense, Collagen Type VI, Biology, leaky splicing, Muscular Dystrophies, 03 medical and health sciences, Exon, 0302 clinical medicine, type VI collagen, Collagen VI, Internal medicine, fibroblasts, medicine, Missense mutation, Humans, Sibling, Myopathy, collagenopathy, Bethlem myopathy, Infant, Exons, Middle Aged, medicine.disease, contractures, Introns, 030104 developmental biology, Endocrinology, Phenotype, Neurology, Biological Variation, Population, myosclerotic phenotype of Bethlem myopathy, Mutation, Neurology (clinical), medicine.symptom, 030217 neurology & neurosurgery |
| الوصف: | International audience; 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. |
| اللغة: | English |
| تدمد: | 2214-3602 2214-3599 4740-2679 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::be2f1397fdf700dced3ab8143a7c49f6 http://europepmc.org/articles/PMC8075389 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....be2f1397fdf700dced3ab8143a7c49f6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22143602 22143599 47402679 |
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