Abhiraami Kannan-Sundhari1,2, Denise Yan1, Kolsoum Saeidi3,4, Afsaneh Sahebalzamani5, Susan H Blanton1,2,6, Xue Zhong Liu1,2,6. 1. Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USA. 2. Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA. 3. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. 4. Department of Medical Genetics, Kerman University of Medical Sciences, Kerman, Iran. 5. Genetic Counselling Center, Welfare Organization of Kerman, Kerman, Iran. 6. John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Abstract
Background: Hearing loss (HL) is one of the most common and genetically heterogeneous sensory disorders in humans. Genetic causes underlie 50-60% of all HL and the majority of these cases exhibit an autosomal recessive model of inheritance. Methods: In our study, we used our targeted custom MiamiOtoGenes panel of 180 HL-associated genes to screen 23 unrelated consanguineous Iranian families with at least two affected children to identify potential causal variants for HL. Results: We identified pathogenic variants in seven genes (MYO7A, CDH23, GIPC3, USH1C, CAPB2, LOXHD1, and STRC) in nine unrelated families with varying HL profiles. These include five reported and four novel mutations. Conclusion: For small consanguineous families that were unsuitable for conventional linkage analysis the employment of the MiamiOtoGenes panel helped identify the genetic cause of HL in a cost-effective and timely manner. This rapid methodology provides for diagnoses of a significant fraction of HL patients, and identifies those who will need more extensive genetic analyses such as whole exome/genome sequencing.
Background: Hearing loss (HL) is one of the most common and genetically heterogeneous sensory disorders in humans. Genetic causes underlie 50-60% of all HL and the majority of these cases exhibit an autosomal recessive model of inheritance. Methods: In our study, we used our targeted custom MiamiOtoGenes panel of 180 HL-associated genes to screen 23 unrelated consanguineous Iranian families with at least two affected children to identify potential causal variants for HL. Results: We identified pathogenic variants in seven genes (MYO7A, CDH23, GIPC3, USH1C, CAPB2, LOXHD1, and STRC) in nine unrelated families with varying HL profiles. These include five reported and four novel mutations. Conclusion: For small consanguineous families that were unsuitable for conventional linkage analysis the employment of the MiamiOtoGenes panel helped identify the genetic cause of HL in a cost-effective and timely manner. This rapid methodology provides for diagnoses of a significant fraction of HL patients, and identifies those who will need more extensive genetic analyses such as whole exome/genome sequencing.
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