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Aberrant COL11A1 splicing causes prelingual autosomal dominant nonsyndromic hearing loss in the DFNA37 locus
Author(s) -
Rad Aboulfazl,
SchadeMann Thore,
Gamerdinger Philipp,
Yanus Grigoriy A.,
Schulte Björn,
Müller Marcus,
Imyanitov Evgeny N.,
Biskup Saskia,
Löwenheim Hubert,
Tropitzsch Anke,
Vona Barbara
Publication year - 2021
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24136
Subject(s) - splice , biology , genetics , hearing loss , locus (genetics) , rna splicing , splice site mutation , gene , audiology , medicine , rna
Alpha‐chain collagen molecules encoded by genes that include COL11A1 are essential for skeletal, ocular, and auditory function. COL11A1 variants have been reported in syndromes involving these organ systems. However, a description of the complete clinical spectrum is lacking, as evidenced by a recent association of autosomal dominant nonsyndromic hearing loss due to a splice‐altering variant in COL11A1 , mapping the DFNA37 locus. Here, we describe two German families presenting prelingual autosomal dominant nonsyndromic hearing loss with novel COL11A1 heterozygous splice‐altering variants (c.652‐1G>C and c.4338+2T>C) that were molecularly characterized. Interestingly, the c.652‐1G>C variant affects the same intron 4 canonical splice site originally reported in the DFNA37 family (c.652‐2A>C) but elicits a different splicing outcome. Furthermore, the c.4338+2T>C variant originated de novo. We provide clinical and molecular genetic evidence to unambiguously confirm that COL11A1 splice‐altering variants cause DFNA37 hearing loss and affirm that COL11A1 be included in the genetic testing of patients with nonsyndromic deafness.