Abstract
Autosomal dominant nonsyndromic hearing loss (ADNSHL) is extremely heterogeneous. So far the genetic etiological contribution of the gene POU4F3 associated with ADNSHL has been rarely reported. In our previous study, a c.603_604delGG mutation in the hair cell specific gene POU4F3 has been identified as the pathogenic cause in one of the seven Chinese Han ADNSHL families. In the present study, we performed targeted next-generation sequencing of 144 known deafness genes in another nine Chinese Han ADNSHL families and identified two more novel mutations in POU4F3, p.Leu311Pro and c.120+1G>C, as the pathogenic cause. Clinical characterization of the affected individuals in these three families showed that the three POU4F3 mutations may lead to progressive hearing loss with variable ages of onset and degrees of severity. Our results suggested that mutations in POU4F3 are a relatively common cause (3/16) for ADNSHL in Chinese Hans, which should be routinely screened in such cases during genetic testing.
Highlights
Hearing loss is one of the most common sensorineural defects, which may result from a great variety of genetic and environmental factors
POU4F3 Mutations Identified in the Autosomal dominant nonsyndromic hearing loss (ADNSHL) Families
In our previous studies of 7 Chinese Han ADNSHL families, a c.603 604delGG (p.Leu201fs∗12) mutation in POU4F3 has been identified by targeted nextgeneration sequencing (NGS) as the pathogenic cause in Family P59 [18]
Summary
Hearing loss is one of the most common sensorineural defects, which may result from a great variety of genetic and environmental factors. Based on the inheritance patterns, the genetic hearing loss can be classified into autosomal recessive, autosomal dominant, and X-linked/mitochondrial, accounting for approximately 80%, 15%, and less than 5% of nonsyndromic hearing loss, respectively [1]. Both autosomal dominant (ADNSHL) and autosomal recessive (ARNSHL) nonsyndromic hearing loss have an extremely high degree of heterogeneity. For the former, 35 causative genes and over 60 loci have been reported for ADNSHL (The hereditary Hearing Loss Homepage, http://hereditaryhearingloss.org/). The development of nextgeneration sequencing (NGS) has complemented the traditional Sanger sequencing method and made it possible to screen all deafness-associated genes in a high throughout manner [2,3,4]
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