Genetic and molecular analysis of the CLDN14 gene in Moroccan family with non-syndromic hearing loss

Abstract

BACKGROUND:Hearing loss is the most prevalent human genetic sensorineural defect. Mutations in the CLDN14 gene, encoding the tight junction claudin 14 protein expressed in the inner ear, have been shown to cause non-syndromic recessive hearing loss DFNB29.AIM:We describe a Moroccan SF7 family with non-syndromic hearing loss. We performed linkage analysis in this family and sequencing to identify the mutation causing deafness.MATERIALS AND METHODS:Genetic linkage analysis, suggested the involvement of CLDN14 and KCNE1 gene in deafness in this family. Mutation screening was performed using direct sequencing of the CLDN14 and KCNE1 coding exon gene.RESULTS:Our results show the presence of c.11C>T mutation in the CLDN14 gene. Transmission analysis of this mutation in the family showed that the three affected individuals are homozygous, whereas parents and three healthy individuals are heterozygous. This mutation induces a substitution of threonine to methionine at position 4.CONCLUSION:These data show that CLDN14 gene can be i mplicated in the development of hearing loss in SF7 family; however, the pathogenicity of c.11C>T mutation remains to be determined.

The Segregation of p.Arg68Ter-CLDN14 Mutation in a Syrian Deaf Family, Phenotypic Variations, and Comparative Analysis with the GJB2 Gene

“…So far, fourteen mutations in the CLDN14 gene have been associated with ARSNHL [3,[7][8][9][10][11][12][13][14][15][16][17]. The highest contribution and number of mutations have been reported in the Pakistani population, where the prevalence of CLDN14 pathogenic variants was estimated to be 2.25% of deaf individuals [7].…”

“…The highest contribution and number of mutations have been reported in the Pakistani population, where the prevalence of CLDN14 pathogenic variants was estimated to be 2.25% of deaf individuals [7]. It is worth noting that even though there is phenotypic variability associated with certain mutations, the impact of CLDN14 mutations tends to be more severe at higher frequencies, with moderate to severe phenotypes reported at low frequencies, while severe to profound phenotypes often exhibited at higher frequencies [3,7,8,[10][11][12][13][14].…”

Usher Syndrome and Its Genetic Characterization

“…Mouse models: For many reasons it is often difficult to identify the genetic factors that are responsible for different forms of hearing loss in humans [17]. Large families with several hearing-impaired members are required for Genetic linkage analysis of hereditary hearing loss in humans [18]. Linkage analysis in small families with hearing impairment leads to difficulty in positional cloning [19].…”