Clinical and Molecular Profiles of a Cohort of Egyptian Patients with Collagen VI-Related Dystrophy.

Autor: Sharaf-Eldin WE; Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Rafat K; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, 12311, Egypt., Issa MY; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, 12311, Egypt., Elbendary HM; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, 12311, Egypt., Eissa NR; Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Hawaary B; Pediatrics Department, Faculty of Medicine, Aswan University, Aswan, Egypt., Gaboon NEA; Medical Genetics Centre, Faculty of Medicine, Ain Shams University, Cairo, Egypt.; Medical Genetics Department, Armed Forces College of Medicine, Cairo, Egypt., Maroofian R; Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK., Gleeson JG; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA.; Rady Children's Institute for Genomic Medicine, San Diego, La Jolla, CA, 92093, USA., Essawi ML; Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Zaki MS; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, 12311, Egypt. dr_mahazaki@yahoo.com.; Medical Genetics Department, Armed Forces College of Medicine, Cairo, Egypt. dr_mahazaki@yahoo.com.
Jazyk: angličtina
Zdroj: Journal of molecular neuroscience : MN [J Mol Neurosci] 2024 Oct 05; Vol. 74 (4), pp. 93. Date of Electronic Publication: 2024 Oct 05.
DOI: 10.1007/s12031-024-02266-8
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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