Uncommon cytidine-homopolymer dimorphism in 5'-UTR of the human otoferlin gene.

Human otoferlin, homologous to the Caenorhabditis elegans spermatogenesis factor FER-1 that was shown to be involved in membrane vesicle fusion, belongs to a group of membrane-anchored cytosolic proteins and is found expressed in brain, cochlear inner hair cells and vestibular type I sensory cells. Nonsense and missense mutations of OTOF lead to an autosomal recessive deafness phenotype (DFNB9). We describe here an unusual C-homopolymer dimorphism at position -136 of 5'-UTR of the OTOF short splice form. Although at first identified within a family with a hereditary component of hearing deficiency this C3/C5 dimorphism is found frequently in European populations (0.4 for C3, 0.6 for C5) and does not segregate with the deafness phenotype. The polymorphic site may become useful for studying the origin of different OTOF mutations within various populations, for assessing recombination events within large pedigrees as well as founder effects and for association studies in further deafness phenotypes.