Congenital profound deafness affects 0.05-0.1% of children in the United States. In most of these families, there is no history of hearing loss, and in the deaf child, a definitive etiology is only rarely established. The majority of cases are ascribed to unknown, or presumed, genetic factors. Estimates of the proportion of deafness due to genetic factors vary from 20-76%. Recent advances in the molecular genetics of deafness have improved our ability to identify heritable hearing losses. Most familial moderate-to-profound congenital losses are inherited as an autosomal recessive trait. Heterogeneity is high, and to date, 28 autosomal recessive non-syndromic hearing loss (ARNSHL) loci have been identified. Six relevant genes also have been cloned. Interestingly, and unexpectedly, mutations in one gene, GJB2, have been found to be responsible for half of moderate-to-profound ARNSHL in multiplex families in many countries worldwide. These discoveries have several important and immediate consequences. First, we are beginning to understand auditory physiology at the molecular level; second, it is now possible to study relationships between genotype, phenotype , and habilitative outcome; and third, genetic testing for congenital deafness is feasible. Complementary research efforts must address these issues. This competing continuation will advance our understanding of ARNSHL with specific aims to localize and clone novel ASNSHL genes, to clone the DFNB7/11 gene, to compare genotype, phenotype and habilitative outcome in various cohorts of children with severe-to-profound ARNSHL, and to determine whether there is a role for genetic testing as a complement to newborn hearing screening in the state of Iowa.
| Booth, K T; Kahrizi, K; Babanejad, M et al. (2018) Variants in CIB2 cause DFNB48 and not USH1J. Clin Genet 93:812-821 |
| Booth, Kevin T; Kahrizi, Kimia; Najmabadi, Hossein et al. (2018) Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment. J Med Genet 55:555-560 |
| Avenarius, Matthew R; Jung, Jae-Yun; Askew, Charles et al. (2018) Grxcr2 is required for stereocilia morphogenesis in the cochlea. PLoS One 13:e0201713 |
| Booth, Kevin T; Askew, James W; Talebizadeh, Zohreh et al. (2018) Splice-altering variant in COL11A1 as a cause of nonsyndromic hearing loss DFNA37. Genet Med : |
| Azaiez, Hela; Booth, Kevin T; Ephraim, Sean S et al. (2018) Genomic Landscape and Mutational Signatures of Deafness-Associated Genes. Am J Hum Genet 103:484-497 |
| Imtiaz, Ayesha; Belyantseva, Inna A; Beirl, Alisha J et al. (2018) CDC14A phosphatase is essential for hearing and male fertility in mouse and human. Hum Mol Genet 27:780-798 |
| Booth, Kevin T; Azaiez, Hela; Kahrizi, Kimia et al. (2018) Exonic mutations and exon skipping: Lessons learned from DFNA5. Hum Mutat 39:433-440 |
| Michel, Vincent; Booth, Kevin T; Patni, Pranav et al. (2017) CIB2, defective in isolated deafness, is key for auditory hair cell mechanotransduction and survival. EMBO Mol Med 9:1711-1731 |
| Shearer, A Eliot; Eppsteiner, Robert W; Frees, Kathy et al. (2017) Genetic variants in the peripheral auditory system significantly affect adult cochlear implant performance. Hear Res 348:138-142 |
| Lansdon, L A; Bernabe, H V; Nidey, N et al. (2017) The Use of Variant Maps to Explore Domain-Specific Mutations of FGFR1. J Dent Res 96:1339-1345 |
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