Reclassification of a TMC1 synonymous substitution as a variant disrupting splicing regulatory elements associated with recessive hearing loss.

ABSTRACT: Alterations of the transmembrane channel-like 1 gene (TMC1) are involved in autosomal recessive and dominant nonsyndromic hearing loss (NSHL). To date, up to 117 causal variants including substitutions, insertions and splice variants have been reported in families from different populations. In a patient suffering from severe prelingual NSHL, we identified, in the homozygous state, the previously considered likely benign synonymous c.627C>T; p.(Leu209=) substitution. We used in silico tools predicting variant-induced alterations of splicing regulatory elements (SREs) and pinpointed this transition as a candidate splice-altering variation. Functional splicing analysis, using a minigene assay, confirmed that the variant altered a critical regulatory sequence which is essential for the exon 1

SUBMITTER: Vache C 

PROVIDER: S-EPMC8738754 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature