The first case of NSHL by direct impression on gene and identification of one novel mutation in in the Iranian families.

OBJECTIVES

Targeted next-generation sequencing (NGS) provides a consequential opportunity to elucidate genetic factors in known diseases, particularly in profoundly heterogeneous disorders such as non-syndromic hearing loss (NSHL). Hearing impairments could be classified into syndromic and non-syndromic types. This study intended to assess the significance of mutations in these genes to the autosomal recessive/dominant non-syndromic genetic load among Iranian families.

MATERIALS AND METHODS

Two families were involved in this research and two patients were examined by targeted next-generation sequencing. Here we report two novel mutations in the and genes in two patients detected by targeted NGS. They were confirmed by Sanger sequencing and quantitative real-time PCR techniques.

RESULTS

In this investigation, we identified a novel mutation in , c.3751G>C, p.A1251P, along with another previously identified mutation (c.1708C>T) in one of the cases. This mutation is located in the MYTH4 protein domain which is a pivotal domain for the myosin function. Another finding in this research was a novel de-novo deletion which deletes the entire coding region (EX1-18 DEL). Mutations in gene have been found in branchiootorenal (BOR) syndrome. Interestingly the patient with EYA1 deletion did not show any other additional clinical implications apart from HL. This finding might argue for the sole involvement of function in the mechanism of hearing.

CONCLUSION

This investigation exhibited that the novel mutations in , c.3751G>C, p.A1251P, and , EX1-18 DEL, were associated with NSHL. Our research increased the mutation spectrum of hearing loss in the Iranian population.