Digenic inheritance of non-syndromic hearing loss caused by novel mutations at MYO3A and DIABLO genes

Hearing loss (HL) is known as a most common sensorineural disorder affecting approximately 2 in 1000 neonates. Genetic factors are involved 50% of the all HL cases. The aim of this study was to explore the genetic factors of HL in two affected sisters derived from consanguineous marriage throughout an Iranian family from Semnan province. Targeted sequencing using Next Generation Illumina Sequencing was used to enrich all exons of 154 genes causing deafness. Subsequently, Sanger sequencing was used for confirmation of mutations found. The obtained results showed a novel stopgain mutation (c.C3154T:p.R1052X) in the MYO3A gene and a novel missense mutation (c.G235A:p.A79T) in the DIABLO gene of proband studied. Mutations in MYO3A and DIABLO genes are associated with nonsyndromic deafness-30 and young-adult onset of nonsyndromic deafness-64, respectively. A detailed analysis of the phenotypes and haplotypes shared by the affected sisters supported the notion that two genes segregated together with hearing impairment in the family suggesting the digenic inheritance pattern of HL. In addition, her consanguineous parents were heterozygote for either MYO3A or DIABLO genes. In overall, this study uncovered two rare novel stopgain and missense mutations causing HL of affected siblings in a digenic mode of inheritance. Such studies may help to conduct genetic counseling and prenatal diagnosis more accurately for individuals at the high risk of this type of HL.

کلیدواژه ها:

Hearing loss ، Digenic inheritance ، Mutation ، MYO3A ، DIABLO.