Identification of pathogenic mechanisms of COCH mutations, abolished cochlin secretion, and intracellular aggregate formation: genotype-phenotype correlations in DFNA9 deafness and vestibular disorder.

ABSTRACT: Mutations in COCH (coagulation factor C homology) cause autosomal-dominant nonsyndromic hearing loss with variable degrees of clinical onset and vestibular malfunction. We selected eight uncharacterized mutations and performed immunocytochemical and Western blot analyses to track cochlin through the secretory pathway. We then performed a comprehensive analysis of clinical information from DFNA9 patients with all 21 known COCH mutations in conjunction with cellular and molecular findings to identify genotype-phenotype correlations. Our studies revealed that five mutants were not secreted into the media: two von Willebrand factor A (vWFA) domain mutants, which were not transported from the endoplasmic reticulum to Golgi complex and formed high-molecular-weight aggregates in cell lysates, and

SUBMITTER: Bae SH 

PROVIDER: S-EPMC4373469 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature