Whole exome sequencing diagnosing syndromic and non-syndromic hearing loss with expansion of the phenotypic spectrum related to TMC1 variants

Hearing loss (HL) is an impending disorder. The high incidence of congenital genetic HL affects the language and communication skills of a large number of children worldwide. Our study is mainly concerned with exploring the genetic etiology of congenital hearing loss through Sanger sequencing of the coding exon in GJB2, the most common causative gene worldwide, in 17 patients from 13 unrelated families followed by whole exome sequencing for cases showing biallelic wildtype GJB2. Eleven patients from eight families showed homozygous and compound heterozygous variants in the GJB2 gene. Six patients from five families proceeded to whole exome sequencing. One of them showed a reported variant in ILDR1, and three showed novel variants in the TMC1 and KCNQ1 genes. Two showed variants reported for the first time in HL patients in the PEX6 and MYO3A genes.In conclusion, this study suggests new insights into the contribution of MYO3A, KCNQ1, and PEX6 to congenital sensorineural hearing loss as well as possible expansion of the phenotypic spectrum of the TMC1 gene. What is Known: • Sanger sequencing and whole exome sequencing are used for molecular diagnosis of syndromic and non-syndromic types of hearing loss (HL). • TMC1 gene causes a type of non-syndromic HL. What is New: • Expanding the molecular spectrum of MYO3A, PEX6, TMC1, and KCNQ1 genes as contributor genes in HL by detecting variants first time to be detected in HL patients. • Expanding the clinical spectrum of TMC1 gene to cause syndromic and non-syndromic HL.