Next generation sequencing and genetics of hereditary hearing loss in the iranian population: New insights from a systematic review.

BACKGROUND

Hereditary hearing loss (HL) as a common disorder is genetically heterogeneous, which poses a challenge for clinical and molecular diagnosis. Next-generation sequencing (NGS) technologies have proven to be the best solution for mutational screening, even though it is not always conclusive. Here, we have reviewed the results of previously published data on HL mutations identified with NGS, as well as the efficiency of this technology in detecting HL in Iran.

METHODS

A systematic literature review of the PubMed, Google Scholar, Web of Science, and Science Direct databases were conducted for articles published before May 2019. The primary data of these studies, including the number of samples, mutation frequency and so on were extracted.

RESULTS

Seventy-five articles were reviewed, and 10 met our inclusion criteria. Totally 432 unrelated families were included and analyzed for the type and prevalence of the gene mutations and pathogenic variants were discovered in 34 non-syndromic HL (NSHL) genes. Altogether 237 different genetic mutations were detected. However, p. Gln1576Stop in PCDH15 was the most common mutation accounting for 1% of the populations studied. NGS platforms have yielded only a 47.1% molecular diagnosis rate for NSHL etiologies in the Iranian population, which is significantly lower than that identified in the other part of the Middle East.

CONCLUSION

The results showed that NGS platforms can greatly assist and enhance HL diagnosis and improve molecular diagnostic outcome. However, researchers were unable to provide 53% of their Iranian cohort with a molecular diagnosis for their HL. It seems that many rare genes are responsible for the majority of HL in the Iranian cohort. Future explorative investigations utilizing NGS technologies, such as WES, into the Iranian population are warranted.