Genetics of Nonsyndromic Congenital Hearing Loss

Abstract

Congenital hearing impairment affects nearly 1 in every 1000 live births and is the most frequent birth defect in developed societies. Hereditary types of hearing loss account for more than 50% of all congenital sensorineural hearing loss cases and are caused by genetic mutations. HL can be either nonsyndromic, which is restricted to the inner ear, or syndromic, a part of multiple anomalies affecting the body. Nonsyndromic HL can be categorised by mode of inheritance, such as autosomal dominant (called DFNA), autosomal recessive (DFNB), mitochondrial, and X-linked (DFN). To date, 125 deafness loci have been reported in the literature: 58 DFNA loci, 63 DFNB loci, and 4 X-linked loci. Mutations in genes that control the adhesion of hair cells, intracellular transport, neurotransmitter release, ionic hemeostasis, and cytoskeleton of hair cells can lead to malfunctions of the cochlea and inner ear. In recent years, with the increase in studies about genes involved in congenital hearing loss, genetic counselling and treatment options have emerged and increased in availability. This paper presents an overview of the currently known genes associated with nonsyndromic congenital hearing loss and mutations in the inner ear.

A de novo interstitial deletion of 7q31.2q31.31 identified in a girl with developmental delay and hearing loss

“…It is interesting to notice that these genes encode proteins with diverse functions, including cytoskeleton proteins, cell–cell junction proteins, transporters, and ion channels. Yet more causative genes for deafness remain to be discovered [Shearer and Smith, ; Egilmez and Kalcioglu, ].…”

Moderate-Severe Hearing Loss in Children: A Diagnostic and Rehabilitative Challenge

“…Because of the improved diagnostic techniques, about 160 genes have been linked to hearing impairment so far. Many genes have been discovered to be involved in auditory function: mutations of proteins implicated in adhesion between hair cells, ionic transport, neurotransmitter release, and cytoskeletons of inner ear cells may be linked to cochlear disorders [33] . An updated official database of recognized monogenic non-syndromic types of hearing loss is available at the Hereditary Hearing Loss Homepage (http://hereditaryhearingloss.org/) [34] .…”

Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome

“…sequencing of the EPHA2 gene in 40 Japanese hearing loss patients with EVA carrying mono-allelic mutation of SLC26A4 were examined. While mutation of~70 genes causing hearing loss were previously identified as a human nonsyndromic deafness gene39 , they were not identified in these patients40 . On the other hand, two missense mutations of the EPHA2 gene were identified in two families, SLC26A4: c.1300G>A (p.434A>T), EPHA2: c.1063G>A (p.G355R) and SLC26A4: c.1229C>A (p.410T>M), EPHA2: c.1532C>T (p.T511M)…”