A novel variant in the COL6A1 gene causing Ullrich congenital muscular dystrophy in a consanguineous family: a case report.

Autor: Sirisena ND; Human Genetics Unit, Department of Anatomy, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka. nirmala@anat.cmb.ac.lk., Samaranayake UMJE; Human Genetics Unit, Department of Anatomy, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka., Neto OLA; Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, NINDS, National Institutes of Health, Bethesda, USA., Foley AR; Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, NINDS, National Institutes of Health, Bethesda, USA., Pathirana BAPS; Human Genetics Unit, Department of Anatomy, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka., Neththikumara N; Human Genetics Unit, Department of Anatomy, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka., Paththinige CS; Human Genetics Unit, Department of Anatomy, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.; Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Anuradhapura, 50008, Sri Lanka., Rathnayake P; Lady Ridgeway Hospital for Children, Colombo 8, Sri Lanka., Donkervoort S; Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, NINDS, National Institutes of Health, Bethesda, USA., Bönnemann CG; Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, NINDS, National Institutes of Health, Bethesda, USA., Dissanayake VHW; Human Genetics Unit, Department of Anatomy, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.
Jazyk: angličtina
Zdroj: BMC neurology [BMC Neurol] 2021 Mar 09; Vol. 21 (1), pp. 105. Date of Electronic Publication: 2021 Mar 09.
DOI: 10.1186/s12883-021-02134-7
Abstrakt: Background: Collagen VI-related dystrophies are a subtype of congenital muscular dystrophy caused by pathogenic variants in COL6A1, COL6A2 or COL6A3 genes affecting skeletal muscles and connective tissue. The clinical phenotype ranges from the milder Bethlem myopathy to the severe Ullrich congenital muscular dystrophy (UCMD). Herein, we report the first consanguineous Sri Lankan family with two children affected with UCMD due to a novel variant in the COL6A1 gene.
Case Presentation: Two sisters, aged 10-years and 7-years, presented with progressive, bilateral proximal muscle weakness. Both probands had delayed motor milestones and demonstrated difficulty in standing from a squatting position, climbing stairs and raising arms above the shoulders. Cognitive, language and social development were age appropriate. Examination showed proximal muscle weakness of the upper and lower extremities and hyperlaxity of the wrist and fingers in both with some variability in clinical severity noted between the two siblings. Serum creatine kinase levels were elevated, and electromyography showed low polyphasic motor unit potentials in the 10-year-old and myopathic features with short duration motor unit potentials with no polyphasia in the 7-year-old. Whole exome sequencing (WES) was performed and a novel, homozygous missense, likely pathogenic variant in exon 25 of COL6A1 gene [NM_001848: c.1667G > T;NP_001839.2:p.Gly556Val] was identified in both probands. This variant was validated by Sanger sequencing in proband 1 as well as proband 2, and the parents and an unaffected sibling were found to be heterozygote carriers for the same variant.
Conclusions: The findings in this family add to the expanding number of COL6A1 variants identified and provides a better understanding of the genotype-phenotype correlations associated with UCMD.
Databáze: MEDLINE
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