Novel OTOF gene mutations identified using a massively parallel DNA sequencing technique in DFNB9 deafness

Objectives: This study examined the causative genes in patients with early-onset hearing loss from two Chinese families. Method: Massively parallel sequencing, designed to screen all reported genes associated with hearing loss, was performed in a large number of Chinese individuals with hearing loss. This study enrolled patients with the same OTOF mutation and analyzed their phenotype-genotype correlations. Results: Three novel OTOF mutations (NM_001287489) [c.1550T> C (p.L517P), c.5900_5902delTCA (p.l1967del), and c.4669_4677deICTGACGGTG (p.L.1557-V1559del)] were found to be the cause of hearing loss in five patients. In family AH-890, the affected subject homozygous for p.L517P presented with profound hearing loss, while the affected sisters compound heterozygous for p.L517P and p.11967del had mild-to-moderate hearing loss. The patient with hearing loss in family SD-345 was found to be compound heterozygous for p.L517P and p.L1557-V1559del. Conclusion: Three presumably pathogenic mutations in the OTOF gene were detected for the first time, including the first pathogenic mutation detected in the TM domain. In addition to expanding the spectrum of OTOF mutations resulting in DFNB9, our findings present the diversity of its clinical presentation and indicate that MPS is an efficient approach to identify the causative genes associated with hereditary hearing loss.