title: Molecular analysis of the GATA3 gene in five Japanese patients with HDR syndrome.
abstract: GATA3 is a member of the GATA family of transcription factors. Heterozygous GATA3 abnormalities are associated with hypoparathyroidism, sensorineural deafness, and renal abnormality (HDR syndrome). However, this triad of symptoms does not occur in all HDR patients and other clinical features may be present in some cases. We report the clinical phenotypes and the molecular analysis of GATA3 in five Japanese HDR patients, including two familial cases. All five patients had hypoparathyroidism and sensorineural deafness, however renal abnormalities were absent in four patients. In addition, two patients with different mutations of GATA3 had female genital tract abnormalities. Sequence analysis of GATA3 demonstrated three novel (R262G, c1063delC and C318) and two reported mutations (c.432insG and c.1051-1G>T). Transient transfection assay using the GATA3 activating reporter system revealed that the transactivating activity of the R262G, c.1063delC, C318S and c.432insG mutants were markedly decreased, indicating that all four mutations are loss-of-function. In conclusion, this study reiterates the clinical variability in HDR syndrome and identifies three novel mutations of GATA3.
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan. akieda@med.hokudai.ac.jp
authors.forename: Akie
authors.initials: A
authors.lastname: Nakamura
authors.forename: Fumie
authors.initials: F
authors.lastname: Fujiwara
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Katsura
authors.initials: K
authors.lastname: Ishizu
authors.forename: Akiyo
authors.initials: A
authors.lastname: Mabe
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagasaki
authors.forename: Wakako
authors.initials: W
authors.lastname: Jo
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004247:DNA / Q000032:analysis; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics*; D005836:Genitalia, Female / Q000002:abnormalities; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007011:Hypoparathyroidism / Q000175:diagnosis / Q000235:genetics; D007223:Infant; D007564:Japan; D007668:Kidney / Q000002:abnormalities; D008297:Male; D009401:Nephrosis / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D050990:GATA3 Transcription Factor; D004247:DNA