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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
Project #
Application #
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Watson, Bracie
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Miami School of Medicine
Schools of Medicine
Coral Gables
United States
Zip Code
Bademci, G; Cengiz, F B; Foster Ii, J et al. (2016) Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss. Sci Rep 6:31622
Grati, M'hamed; Yan, Denise; Raval, Manmeet H et al. (2016) MYO3A Causes Human Dominant Deafness and Interacts with Protocadherin 15-CD2 Isoform. Hum Mutat 37:481-7
Manzoli, Gabrielle N; Bademci, Guney; Acosta, Angelina X et al. (2016) Targeted Resequencing of Deafness Genes Reveals a Founder MYO15A Variant in Northeastern Brazil. Ann Hum Genet 80:327-331
Tekin, Demet; Yan, Denise; Bademci, Guney et al. (2016) A next-generation sequencing gene panel (MiamiOtoGenes) for comprehensive analysis of deafness genes. Hear Res 333:179-84
Yao, Qi; DeSmidt, Alexandra A; Tekin, Mustafa et al. (2016) Hearing Assessment in Zebrafish During the First Week Postfertilization. Zebrafish 13:79-86
Bademci, Guney; Foster 2nd, Joseph; Mahdieh, Nejat et al. (2016) Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort. Genet Med 18:364-71
Ben Said, Mariem; Grati, M'hamed; Ishimoto, Takahiro et al. (2016) A mutation in SLC22A4 encoding an organic cation transporter expressed in the cochlea strial endothelium causes human recessive non-syndromic hearing loss DFNB60. Hum Genet 135:513-24
Diaz-Horta, Oscar; Abad, Clemer; Sennaroglu, Levent et al. (2016) ROR1 is essential for proper innervation of auditory hair cells and hearing in humans and mice. Proc Natl Acad Sci U S A 113:5993-8
Atik, Tahir; Bademci, Guney; Diaz-Horta, Oscar et al. (2015) Whole-exome sequencing and its impact in hereditary hearing loss. Genet Res (Camb) 97:e4
Atik, Tahir; Koparir, Asuman; Bademci, Guney et al. (2015) Novel MASP1 mutations are associated with an expanded phenotype in 3MC1 syndrome. Orphanet J Rare Dis 10:128

Showing the most recent 10 out of 36 publications