A Novel Locus Harbouring a Functional Nonsense Mutation Identified in a Large Danish Family with Nonsyndromic Hearing Impairment

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It is known that hearing impairment running in families can be caused by mutations in more than eighty different genes. However, there are still families where the responsible gene is unknown. By studying a large Danish family with dominant inherited hearing impairment, we found that the disorder cosegregates with genetic markers on chromosome 6, suggesting that the responsible mutation lies within this chromosomal region. By sequencing this genetic locus, we discovered a mutation in the CD164 gene that is passed on to all the affected individuals. In the mouse ear, we demonstrated that the CD164 protein is expressed in hair cells and other sites known to be important for correct hearing. The identified mutation is predicted to result in shortening of the protein, leading to loss of an evolutionary conserved sequence important for cellular trafficking of CD164. Using cell lines, we show that the truncated protein is trapped on the cell surface while the normal protein is internalized. This finding is important because it implicates for the first time a role for CD164 in the complex physiological processes of hearing and suggests that failed endocytosis may be a possible disease mechanism for some types of hearing impairment.

Vyšlo v časopise: A Novel Locus Harbouring a Functional Nonsense Mutation Identified in a Large Danish Family with Nonsyndromic Hearing Impairment. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005386
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005386

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