title: Identification of three novel mutations in the GATA3 gene responsible for familial hypoparathyroidism and deafness in the Chinese population.
abstract: BACKGROUND
  Familial hypoparathyroidism may be caused by mutations of several genes. The CaSR and GATA3 genes are the two candidates most commonly responsible for this condition.
  
  
  OBJECTIVE
  We collected five unrelated families with familial hypoparathyroidism and examined their CaSR and GATA3 genes.
  
  
  METHODS
  Blood samples from these five families and 50 ethnically matched unrelated controls were acquired. Biochemistry screening and formal audiogram were performed to evaluate the affected individuals. All the exons and exon-intron boundaries of the GATA3 and CaSR genes were sequenced.
  
  
  RESULTS
  We identified three novel mutations in the GATA3 gene responsible for familial hypoparathyroidism and deafness: 1) a frameshift deletion occurring in codon 160 (478delG) was hypothesized to disrupt dual zinc fingers as well as one transactivating domain; 2) a donor splice site mutation at exon 4/intron 4 boundary (IVS4 + 2 T to GCTTACTTCCC) was predicted to lead to truncated GATA3 proteins that lack both N- and C-terminal zinc-containing fingers; and 3) a missense mutation R353S was predicted to disrupt the helical turn and thus changed the angle between the C-terminal zinc finger and the adjacent C-terminal tail. Except for a previously described polymorphism, G990R, we did not find any genetic variants in the CaSR gene.
  
  
  CONCLUSIONS
  This is the first article presenting mutations of the GATA3 gene responsible for familial hypoparathyroidism and deafness in the Chinese population. Our results expand the spectrum of mutations and report the first splice donor site mutation of the GATA3 gene. In contrast, we do not find causal sequence variants of the CaSR gene from our collection of familial hypoparathyroidism.
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
authors.forename: Wei-Yih
authors.initials: WY
authors.lastname: Chiu
authors.forename: Huan-Wen
authors.initials: HW
authors.lastname: Chen
authors.forename: Hwei-Wen
authors.initials: HW
authors.lastname: Chao
authors.forename: Lee-Tzong
authors.initials: LT
authors.lastname: Yann
authors.forename: Keh-Sung
authors.initials: KS
authors.lastname: Tsai
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000502:physiology; D005828:Genetics, Population; D006801:Humans; D007011:Hypoparathyroidism / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D044169:Receptors, Calcium-Sensing / Q000235:genetics
chemical_list: C095550:CASR protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D044169:Receptors, Calcium-Sensing