title: Clinical Auditory Phenotypes Associated withGATA3Gene Mutations in Familial Hypoparathyroidism-deafness-renal Dysplasia Syndrome.
abstract: BACKGROUND
  Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases.
  
  
  METHODS
  Three affected family members underwent otologic examinations, biochemistry tests, and other clinical evaluations. Targeted genes capture combining next-generation sequencing was performed within the family. Sanger sequencing was used to confirm the causative mutation. The auditory phenotypes of all reported familial HDR syndrome cases analyzed were provided.
  
  
  RESULTS
  In Chinese family 7121, a heterozygous nonsense mutation c.826C>T (p.R276*) was identified in GATA3. All the three affected members suffered from sensorineural deafness and hypocalcemia; however, renal dysplasia only appeared in the youngest patient. Furthermore, an overview of thirty HDR syndrome families with corresponding GATA3 mutations revealed that hearing impairment occurred earlier in the younger generation in at least nine familial cases (30%) and two thirds of them were found to carry premature stop mutations.
  
  
  CONCLUSIONS
  This study highlights the phenotypic heterogeneity of HDR and points to a possible genetic anticipation in patients with HDR, which needs to be further investigated.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853; Department of Clinical Medicine, School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Beijing Genomics Institute, Shenzhen, Guangdong 518083, China.
authors.forename: Qiong-Fen
authors.initials: QF
authors.lastname: Lin
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Lan
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Lin-Yi
authors.initials: LY
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Beijing Genomics Institute, Shenzhen, Guangdong 518083, China.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Liang
authors.affiliation: Beijing Genomics Institute, Shenzhen, Guangdong 518083, China.
authors.forename: Han-Lin
authors.initials: HL
authors.lastname: Zhou
authors.affiliation: Beijing Genomics Institute, Shenzhen, Guangdong 518083; James D. Watson Institute of Genome Sciences, Hangzhou, Zhejiang 310058, China.
authors.forename: Huan-Ming
authors.initials: HM
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Xiong
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Qiu-Jing
authors.initials: QJ
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, 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: D002648:Child; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics*; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007011:Hypoparathyroidism / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D009401:Nephrosis / Q000235:genetics*; D010375:Pedigree
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human