ObjectiveAuditory neuropathy spectrum disease (ANSD) is caused by both environmental and genetic causes and is defined by a failure in peripheral auditory neural transmission but normal outer hair cells function. To date, 13 genes identified as potentially causing ANSD have been documented. To study the etiology of ANSD, we collected 9 probands with ANSD diagnosed in the clinic and performed targeted next-generation sequencing.MethodsNine probands have been identified as ANSD based on the results of the ABR tests and DPOAE/CMs. Genomic DNA extracted from their peripheral blood was examined by next-generation sequencing (NGS) for a gene panel to identify any potential causal variations. For candidate pathogenic genes, we performed co-segregation among all family members of the pedigrees. Subsequently, using a mini-gene assay, we examined the function of a novel splice site mutant of OTOF.ResultsWe analyzed nine cases of patients with ANSD with normal CMs/DPOAE and abnormal ABR, discovered three novel mutants of the OTOF gene that are known to cause ANSD, and six cases of other gene mutations including TBC1D24, LARS2, TIMM8A, MITF, and WFS1.ConclusionOur results extend the mutation spectrum of the OTOF gene and indicate that the genetic etiology of ANSD may be related to gene mutations of TBC1D24, LARS2, TIMM8A, MITF, and WFS1.
Hearing loss affecting about 2/1000 newborns is the most common congenital disease. Genetic defects caused approximately 70% of patients who have non-syndromic hearing loss. We recruited 13 Chinese Han deafness families who tested negative for GJB2, SLC26A4, and mitochondrial 12S rRNA. The probands of each family were performed whole-exome sequencing (WES) or targeted next-generation sequencing (NGS) for known deafness genes to study for pathogenic causes. We found four novel mutations of CDH23, one novel mutation of MYO15A, one novel mutation of TMC1, one novel mutation of PAX3, and one novel mutation of ADGRV1, one novel CNV of ADGRV1, and one novel CNV of STRC. Hearing loss is a highly hereditary and heterogeneous disease. The results in the limited samples of this study show that Usher and Waardenburg syndrome-related genes account for a major proportion are strongly associated with Chinese Han hearing loss patients negative for GJB2, SLC26A4, and mitochondrial 12S rRNA, followed by STRC resulting in mild to moderate deafness.
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