Clinical and Molecular Profiles of a Cohort of Egyptian Patients with Collagen VI-Related Dystrophy.
Bethlem myopathy
Collagen VI
Next-generation sequencing
Ullrich congenital muscular dystrophy
Journal
Journal of molecular neuroscience : MN
ISSN: 1559-1166
Titre abrégé: J Mol Neurosci
Pays: United States
ID NLM: 9002991
Informations de publication
Date de publication:
05 Oct 2024
05 Oct 2024
Historique:
received:
30
06
2024
accepted:
11
09
2024
medline:
5
10
2024
pubmed:
5
10
2024
entrez:
4
10
2024
Statut:
epublish
Résumé
Collagen VI-related dystrophies (COL6-RD) display a wide spectrum of disease severity and genetic variability ranging from mild Bethlem myopathy (BM) to severe Ullrich congenital muscular dystrophy (UCMD) and the intermediate severities in between with dual modes of inheritance, dominant and recessive. In the current study, next-generation sequencing demonstrated potential variants in the genes coding for the three alpha chains of collagen VI (COL6A1, COL6A2, or COL6A3) in a cohort of Egyptian patients with progressive muscle weakness (n = 23). Based on the age of disease onset and the patient clinical course, subjects were diagnosed as follows: 12 with UCMD, 8 with BM, and 3 with intermediate disease form. Fourteen pathogenic variants, including 5 novel alterations, were reported in the enrolled subjects. They included 3 missense, 3 frameshift, and 6 splicing variants in 4, 3, and 6 families, respectively. In addition, a nonsense variant in a single family and an inframe variant in 3 different families were also detected. Recessive and dominant modes of inheritance were recorded in 9 and 8 families, respectively. According to ACMG guidelines, variants were classified as pathogenic (n = 7), likely pathogenic (n = 4), or VUS (n = 3) with significant pathogenic potential. To our knowledge, the study provided the first report of the clinical and genetic findings of a cohort of Egyptian patients with collagen VI deficiency. Inter- and intra-familial clinical variability was evident among the study cohort.
Identifiants
pubmed: 39367186
doi: 10.1007/s12031-024-02266-8
pii: 10.1007/s12031-024-02266-8
doi:
Substances chimiques
Collagen Type VI
0
Col6a1 protein, human
0
COL6A3 protein, human
0
COL6A2 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
93Subventions
Organisme : NRC
ID : 12060178
Organisme : NRC
ID : 12060178
Organisme : NRC
ID : 12060178
Organisme : STDF
ID : 33650
Organisme : STDF
ID : 33650
Organisme : STDF
ID : 33650
Organisme : STDF
ID : 33650
Organisme : STDF
ID : 33650
Organisme : STDF
ID : 33650
Informations de copyright
© 2024. The Author(s).
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