title: Identification of Two Disease-causing Genes TJP2 and GJB2 in a Chinese Family with Unconditional Autosomal Dominant Nonsyndromic Hereditary Hearing Impairment.
abstract: BACKGROUND
  There are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI), including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI). Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI.
  
  
  METHODS
  To decipher the genetic code of a Chinese family (family 686) with ADNSHHI, different gene screening techniques have been performed, including linkage analysis, candidate genes screening, high-throughput sequencing and Sanger sequencing. These techniques were done on samples obtained from this family over a period of 10 years.
  
  
  RESULTS
  We identified a pathogenic missense mutation, c. 2081G>A (p.G694E), in TJP2, a gene that plays a crucial role in apoptosis and age-related hearing loss (ARHL). The mutation was co-segregated in this pedigree in all, but not in the two patients who presented with different phenotypes from the other affected family members. In one of the two patients, we confirmed that the compound heterozygosity for p.Y136* and p.G45E in the GJB2 gene may account for the phenotype shown in this patient.
  
  
  CONCLUSIONS
  We identified the co-occurrence of two genetic causes in family 686. The possible disease-causing missense mutation of TJP2 in family 686 presents an opportunity for further investigation into ARHL. It is necessary to combine various genes screening methods, especially for some unconventional cases.
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Zhao
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.forename: Hu
authors.initials: H
authors.lastname: Yuan
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.forename: Lan
authors.initials: L
authors.lastname: Lan
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Otolaryngology-Head and Neck, Chinese People's Liberation Army Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Qiu-Ju
authors.initials: QJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D055815:Young Adult; D062827:Zonula Occludens-2 Protein / Q000235:genetics*
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; C569046:TJP2 protein, human; D062827:Zonula Occludens-2 Protein; D000072259:Connexin 26