Identification of three novel mutations in the GATA3 gene responsible for familial hypoparathyroidism and deafness in the Chinese population.
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.
Chiu
Wei-Yih
WY
Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
Chen
Huan-Wen
HW
Chao
Hwei-Wen
HW
Yann
Lee-Tzong
LT
Tsai
Keh-Sung
KS
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
C095550:CASR protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D044169:Receptors, Calcium-Sensing