Abstract
Tight junctions are cellular junctions that play a major role in the epithelial barrier function. In the inner ear, claudins, occludin, tricellulin, and angulins form the bicellular or tricellular binding of membrane proteins. In these, one type of claudin gene, CLDN14, was reported to be responsible for human hereditary hearing loss, DFNB29. Until now, nine pathogenic variants have been reported, and most phenotypic features remain unclear. In the present study, genetic screening for 68 previously reported deafness causative genes was carried out to identify CLDN14 variants in a large series of Japanese hearing loss patients, and to clarify the prevalence and clinical characteristics of DFNB29 in the Japanese population. One patient had a homozygous novel variant (c.241C>T: p.Arg81Cys) (0.04%: 1/2549). The patient showed progressive bilateral hearing loss, with post-lingual onset. Pure-tone audiograms indicated a high-frequency hearing loss type, and the deterioration gradually spread to other frequencies. The patient showed normal vestibular function. Cochlear implantation improved the patient’s sound field threshold levels, but not speech discrimination scores. This report indicated that claudin-14 is essential for maintaining the inner ear environment and suggested the possible phenotypic expansion of DFNB29. This is the first report of a patient with a tight junction variant receiving a cochlear implantation.
Highlights
The CLDN14 variants are a relatively common cause of recessive hearing loss, which is responsible for 2.25% of Hearing LossHearing loss (HL) patients in a Pakistani study cohort [28], whereas no pathogenic variants were reported from east Asian populations [30,31]
We present a patient with a novel variant in the CLDN14 gene identified from a non-consanguineous family
This is the first report of CLDN14-associated HL in an east Asian population
Summary
Hearing loss (HL) is the most common sensory impairment and is diagnosed in approximately two in every 1000 children [1]. At least 60% of all childhood nonsyndromic sensorineural hearing loss is caused by genetic factors [2]. The inheritance patterns of this form of HL include autosomal recessive, autosomal dominant, X-linked, and mitochondrial. Autosomal recessive nonsyndromic hereditary HL (ARNSHL) is typically prelingual, and accounts for approximately 70% of nonsyndromic hereditary HL patients [3]. 75 causative genes for ARNSHL have been identified [4]. One form of ARNSHL is DFNB29 (OMIM #: 614035), which is caused by variants in the CLDN14 gene
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