A novel variant in the CDH23 gene is associated with non-syndromic hearing loss in a Chinese family. (January 2018)

• Record Type: Journal Article
• Authors: Liang, Yuan; Wang, Kangwei; Peng, Qi; Zhu, Pengyuan; Wu, Chunqiu; Rao, Chunbao; Chang, Jiang; Li, Siping; Lu, Xiaomei
• Is Part Of: International journal of pediatric otorhinolaryngology. Volume 104(2018:Jan.)
• Page Start: 108
• Page End: 112
• Publication Date: 2018-01
• Subjects: CDH23 -- DFNB12 -- Congenital hearing loss -- Novel variant; Otolaryngology -- Periodicals; Pediatrics -- Periodicals; Otolaryngology -- Periodicals; Pediatrics -- Periodicals; Oto-rhino-laryngologie -- Périodiques; Pédiatrie -- Périodiques; 618.9209751
• DOI: 10.1016/j.ijporl.2017.11.009
• Languages: English
• ISSNs: 0165-5876

Abstract

Abstract: Objectives: To explore the pathogenic causes of a proband who was diagnosed with non-syndromic hearing loss. Methods: We performed targeted capture of 159 known deafness-related genes and next-generation sequencing in the proband who was tested negative for the twenty hotspot variants in four common deafness-related genes( GJB2, GJB3, SLC26A4 and MTRNR1 ); Clinical reassessments, including detailed audiological and ocular examinations were performed in the proband and his normal parents. Results: We identified a novel heterozygous variant of CDH23 :c.4567A > G (p.Asn1523Asp) in exon 37 (NM_022124), in conjunction with a reported mutation of CDH23 :c.5101G > A (p.Glu1701Lys) in exon 40, to be a potentially pathogenic compound heterozygosity in the proband. The unaffected father has a heterozygous variant of CDH23 :c.4567A > G, and the normal mother has another heterozygous variant, CDH23 :c.5101G > A. The novel variant was absent in the 1000 Genomes Project. The clinical reassessments revealed binaural profound sensorineural hearing loss (DFNB12) without retinitis pigmentosa in the proband. Conclusions: This study demonstrates that the novel variant c.4567A > G (p.Asn1523Asp) in compound heterozygosity with c.5101G > A (p. Glu1701Lys) in the CDH23 gene is the main cause of DFNB12 in the proband. Simultaneously, this study provides a foundation to further elucidate the CDH23 -related mechanisms of DFNB12.