Mutations in the gene encoding KIAA1199 protein, an inner-ear protein expressed in Deiters' cells and the fibrocytes, as the cause of nonsyndromic hearing loss.
We report three possibly disease-causing point mutations in one of the inner-ear-specific genes, KIAA1199. We identified an R187C mutation in one family, an R187H mutation in two unrelated families, and an H783Y mutation in one sporadic case of nonsyndromic hearing loss. In situ hybridization indicated that the murine homolog of KIAA1199 mRNA is expressed specifically in Deiters' cells in the organ of Corti at postnatal day zero (P n) P0 before the onset of hearing, but expression in those cells disappears by day P7. The signal of KIAA1199 was also observed in fibrocytes of the spiral ligament and the spiral limbus through to P21, when the murine cochlea matures. Thus, the gene product may be involved in uptake of potassium ions or trophic factors with a particular role in auditory development. Although the R187C and R187H mutations did not appear to affect subcellular localization of the gene product in vitro, the H783Y mutation did present an unusual cytoplasmic distribution pattern that could underlie the molecular mechanism of hearing impairment. Our data bring attention to a novel candidate for hearing loss and indicate that screening of mutations in inner-ear-specific genes is likely to be an efficient approach to finding genetic elements responsible for deafness.
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Satoko
S
Abe
Shin-ichi
S
Usami
Yusuke
Y
Nakamura
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D016022:Case-Control Studies; D003051:Cochlea / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D006821:Hyaluronoglucosaminidase; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009925:Organ of Corti / Q000166:cytology / Q000378:metabolism; D017354:Point Mutation; D011487:Protein Conformation; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment
D011506:Proteins; C491433:CEMIP protein, human; D006821:Hyaluronoglucosaminidase