Journal
HUMAN MUTATION
Volume 42, Issue 1, Pages 25-30Publisher
WILEY-HINDAWI
DOI: 10.1002/humu.24136
Keywords
autosomal dominant hearing loss; DFNA37; nonsyndromic hearing loss; splice‐ site altering variant
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Funding
- Ministerium fur Wissenschaft, Forschung und Kunst Baden-Wurttemberg
- Eberhard Karls Universitat Tubingen [2545-1-0]
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COL11A1-encoded alpha-chain collagen molecules are crucial for skeletal, ocular, and auditory function. Variants in COL11A1 have been associated with syndromes affecting these systems. This study provides evidence that splice-altering variants in COL11A1 cause DFNA37 hearing loss, emphasizing the importance of including COL11A1 in genetic testing for nonsyndromic deafness.
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.
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