Confirmation of COL4A6 variants in X-linked nonsyndromic hearing loss and its clinical implications.

Autor: O'Brien A; Department of Pediatrics, Division of Genetics and Metabolism, UNC Chapel Hill, Chapel Hill, NC, USA., Aw WY; UNC Catalyst For Rare Diseases, UNC Eshelman School of Pharmacy, UNC Chapel Hill, Chapel Hill, NC, USA., Tee HY; UNC Catalyst For Rare Diseases, UNC Eshelman School of Pharmacy, UNC Chapel Hill, Chapel Hill, NC, USA., Naegeli KM; UNC Catalyst For Rare Diseases, UNC Eshelman School of Pharmacy, UNC Chapel Hill, Chapel Hill, NC, USA., Bademci G; Dr. John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA., Tekin M; Dr. John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA., Arnos K; Emeritus, Department of Science, Technology, & Mathematics, Gallaudet University, Washington, DC, USA., Pandya A; Department of Pediatrics, Division of Genetics and Metabolism, UNC Chapel Hill, Chapel Hill, NC, USA. pandya15@email.unc.edu.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2022 Jan; Vol. 30 (1), pp. 7-12. Date of Electronic Publication: 2021 Apr 12.
DOI: 10.1038/s41431-021-00881-2
Abstrakt: Hearing loss (HL) is one of the most common sensory defects, of which X-linked nonsyndromic hearing loss (NSHL) accounts for only 1-2%. While a COL4A6 variant has been reported in a single Hungarian family with NSHL associated with inner ear malformation, causative role of COL4A6 variants and their phenotypic consequences in NSHL remain elusive. Here we report two families in which we identified a male member with X-linked HL. Each has inherited a rare hemizygous COL4A6 variant from their respective mothers, NM_001287758.1: c.3272 G > C (p.Gly1091Ala) and c.951 + 1 G > C. An in vitro minigene splicing assay revealed that c.951 + 1 G > T leads to skipping of exon 15, strongly suggesting a pathogenic role for this variant in the HL phenotype. The p.Gly1091Ala variant is classified as a variant of unknown significance based on the variant interpretation guidelines. This report provides evidence for variants in the COL4A6 gene resulting in X-linked NSHL. It highlights the importance of in-depth genetic studies in all family members in addition to the proband, especially in multiplex families, to determine the precise etiology of HL.
(© 2021. The Author(s), under exclusive licence to European Society of Human Genetics.)
Databáze: MEDLINE
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