Identification of a novel compound heterozygous mutation in PTPRQ in a DFNB84 family with prelingual sensorineural hearing impairment.

With a prevalence of 0.1 %, hearing loss is among the most common sensory impairments and affects several million people around the world. Identification of deafness-related genes or loci may facilitate basic research and clinical translational research of the disorder. The PTPRQ gene encodes protein tyrosine phosphatase receptor Q, which is required for the formation of shaft connectors and the normal maturation and development of hair bundles in the mammalian cochlea. Here, we present the genetic and molecular characteristics of a Kazakh family with an autosomal recessive non-syndromic hearing impairment, DFNB84. Using whole-exome sequencing, we identified two mutations that together form a novel compound heterozygous mutation in PTPRQ. Sanger sequencing confirmed that the affected members inherited both the c.16_17insT (L8fsX18) and c.2714delA (E909fsX922) mutations. Both mutations lead to a frameshift and a truncated form of the protein. The novel compound heterozygous mutation co-segregated with hearing loss in this family, and neither of the two mutations was found in 200 healthy Kazakh controls or in any of the public databases. In the study, we identified novel mutations in PTPRQ responsible for DFNB84. This is the third report of PTPRQ mutations involved in deafness and the first report of familial deafness in China. The identification of novel mutations in PTPRQ presented here further confirms the essential role of PTPRQ in hearing development and auditory function. Our data provide additional molecular information for establishing a better genotype-phenotype understanding of DFNB84.