Novel defects in collagen xii and vi expand ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Novel defects in collagen xii and vi expand the mixed myopathy/ehlers-danlos syndrome spectrum and lead to variant-specific alterations in the extracellular matrix
Auteur(s) :
Delbaere, Sarah [Auteur]
Dhooge, Tibbe [Auteur]
Syx, Delfien [Auteur]
Petit, Florence [Auteur]
Goemans, Nathalie [Auteur]
Destree, Anne [Auteur]
Vanakker, Olivier [Auteur]
De Rycke, Riet [Auteur]
Symoens, Sofie [Auteur]
Malfait, Fransiska [Auteur]
Dhooge, Tibbe [Auteur]
Syx, Delfien [Auteur]
Petit, Florence [Auteur]
Goemans, Nathalie [Auteur]
Destree, Anne [Auteur]
Vanakker, Olivier [Auteur]
De Rycke, Riet [Auteur]
Symoens, Sofie [Auteur]
Malfait, Fransiska [Auteur]
Titre de la revue :
Genetics in medicine . official journal of the American College of Medical Genetics
Nom court de la revue :
Genet. Med.
Date de publication :
2019-07-05
ISSN :
1530-0366
Mot(s)-clé(s) :
collagen VI
connective tissue
myopathy
collagen XII
myopathic Ehlers-Danlos syndrome
connective tissue
myopathy
collagen XII
myopathic Ehlers-Danlos syndrome
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
To date, heterozygous or homozygous COL12A1 variants have been reported in 13 patients presenting with a clinical phenotype overlapping with collagen VI-related myopathies and Ehlers-Danlos syndrome (EDS). The small number ...
Lire la suite >To date, heterozygous or homozygous COL12A1 variants have been reported in 13 patients presenting with a clinical phenotype overlapping with collagen VI-related myopathies and Ehlers-Danlos syndrome (EDS). The small number of reported patients limits thorough investigation of this newly identified syndrome, currently coined as myopathic EDS. DNA from 78 genetically unresolved patients fulfilling the clinical criteria for myopathic EDS was sequenced using a next-generation panel of COL12A1, COL6A1, COL6A2, and COL6A3. Among this cohort, we identified four pathogenic heterozygous in-frame exon skipping (∆) defects in COL12A1, clustering to the thrombospondin N-terminal region and the adjacent collagenous domain (Δ52, Δ53, Δ54, and Δ56 respectively), one heterozygous COL12A1 arginine-to-cysteine substitution of unclear significance (p.(Arg1863Cys)), and compound heterozygous pathogenic COL6A1 variants (c.[98-6G>A];[301C>T]) in one proband. Variant-specific intracellular accumulation of collagen XII chains, extracellular overmodification of the long isoform and near-absence of the short isoform of collagen XII, and extracellular decrease of decorin and tenascin-X were observed for the COL12A1 variants. In contrast, the COL6A1 variants abolished collagen VI and V deposition and increased tenascin-X levels. Our data further support the significant clinical overlap between myopathic EDS and collagen VI-related myopathies, and emphasize the variant-specific consequences of collagen XII defects.Lire moins >
Lire la suite >To date, heterozygous or homozygous COL12A1 variants have been reported in 13 patients presenting with a clinical phenotype overlapping with collagen VI-related myopathies and Ehlers-Danlos syndrome (EDS). The small number of reported patients limits thorough investigation of this newly identified syndrome, currently coined as myopathic EDS. DNA from 78 genetically unresolved patients fulfilling the clinical criteria for myopathic EDS was sequenced using a next-generation panel of COL12A1, COL6A1, COL6A2, and COL6A3. Among this cohort, we identified four pathogenic heterozygous in-frame exon skipping (∆) defects in COL12A1, clustering to the thrombospondin N-terminal region and the adjacent collagenous domain (Δ52, Δ53, Δ54, and Δ56 respectively), one heterozygous COL12A1 arginine-to-cysteine substitution of unclear significance (p.(Arg1863Cys)), and compound heterozygous pathogenic COL6A1 variants (c.[98-6G>A];[301C>T]) in one proband. Variant-specific intracellular accumulation of collagen XII chains, extracellular overmodification of the long isoform and near-absence of the short isoform of collagen XII, and extracellular decrease of decorin and tenascin-X were observed for the COL12A1 variants. In contrast, the COL6A1 variants abolished collagen VI and V deposition and increased tenascin-X levels. Our data further support the significant clinical overlap between myopathic EDS and collagen VI-related myopathies, and emphasize the variant-specific consequences of collagen XII defects.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
Collections :
Date de dépôt :
2021-09-02T07:02:17Z