More than 60% of prelingual deafness is genetic in origin, and of these up to 93% are monogenic autosomal recessive traits. Some forms of genetic deafness can be recognized by their associated syndromic features, but in most cases, hearing loss is the only abnormality. While causal mutations have been identified in one of 31 different genes in a subset of patients with non-syndromic autosomal recessive sensorineural hearing loss, at least 40% of families do not have an identifiable mutation nor do they demonstrate linkage to any known gene. Moreover, the distribution of recognized genetic causes in different populations as well as mutation specific phenotypes remains unknown. Recent advances in molecular technologies provide unprecedented opportunities to genotype dense arrays of SNP markers throughout the genome and to sequence large segments of the human genome with ease. Turkey provides a very valuable resource for the identification of new genes for deafness because it has been continually inhabited since ancient times and much of the population still lives in about 40,000 small villages throughout the country, where consanguinity is the cultural norm. There is also a high level of assortative mating among the deaf and a very long history of the use of sign language in specific areas of Turkey. All of these factors are known to have a profound influence on the survival, expression and spread of new mutations for deafness. We have ascertained 247 inbred multiplex Turkish families with autosomal recessive non-syndromic hearing loss. We will recruit >100 additional families with the same characteristics which will lead to creation of an excellent repository that can be used to identify many of the remaining genes for autosomal recessive non-syndromic deafness. After exclusion of common known genes, we will have ~150 families to discover and confirm new genes for deafness. We will use genome wide dense SNP arrays to find new loci for deafness and identify causative mutations with either traditional or next-generation sequencing. We have already discovered a new deafness gene in one family using the proposed strategy, clearly demonstrating the utility of this invaluable resource. The Repository will be made available to external investigators upon completion of this proposal.
This project is a collaborative study of genetic deafness involving investigators from the United States and Turkey. The goals of the project are to identify new loci and new genes for non-syndromic deafness and to establish a resource for research on genetic deafness including biological samples and clinical data from large numbers of families in Turkey. The outcome of this proposal will expand the scientific knowledge on the genomic basis of hereditary deafness.
| Booth, K T; Kahrizi, K; Babanejad, M et al. (2018) Variants in CIB2 cause DFNB48 and not USH1J. Clin Genet 93:812-821 |
| Masterson, John; Y?ld?r?m, Busegül; Gökkaya, Ece et al. (2018) A Novel Variant in SYNE4 Confirms its Causative Role in Sensorineural Hearing Loss. Balkan Med J 35:196-198 |
| Diaz-Horta, Oscar; Abad, Clemer; Cengiz, Filiz Basak et al. (2018) Ripor2 is involved in auditory hair cell stereociliary bundle structure and orientation. J Mol Med (Berl) 96:1227-1238 |
| Cengiz, Filiz Basak; Yilmazer, Rasim; Olgun, Levent et al. (2017) Novel pathogenic variants underlie SLC26A4-related hearing loss in a multiethnic cohort. Int J Pediatr Otorhinolaryngol 101:167-171 |
| Suba??o?lu, Asl?; Duman, Duygu; S?rmac?, Asl? et al. (2017) Research of genetic bases of hereditary non-syndromic hearing loss. Turk Pediatri Ars 52:122-132 |
| Yan, Denise; Xiang, Guangxin; Chai, Xingping et al. (2017) Screening of deafness-causing DNA variants that are common in patients of European ancestry using a microarray-based approach. PLoS One 12:e0169219 |
| Wesdorp, Mieke; van de Kamp, Jiddeke M; Hensen, Erik F et al. (2017) Broadening the phenotype of DFNB28: Mutations in TRIOBP are associated with moderate, stable hereditary hearing impairment. Hear Res 347:56-62 |
| Menendez, Ibis; Carranza, Claudia; Herrera, Mariana et al. (2017) Dominant deafness-onychodystrophy syndrome caused by an ATP6V1B2 mutation. Clin Case Rep 5:376-379 |
| Klingbeil, Kyle D; Greenland, Christopher M; Arslan, Selcuk et al. (2017) Novel EYA1 variants causing Branchio-oto-renal syndrome. Int J Pediatr Otorhinolaryngol 98:59-63 |
| Tekin, Demet; Yan, Denise; Bademci, Guney et al. (2016) A next-generation sequencing gene panel (MiamiOtoGenes) for comprehensive analysis of deafness genes. Hear Res 333:179-184 |
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