title: GATA3 abnormalities and the phenotypic spectrum of HDR syndrome.
abstract: We report on GATA3 analysis and the phenotypic spectrum in nine Japanese families with the HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) (MIM 146255). Fluorescence in situ hybridisation and microsatellite analyses showed heterozygous gross deletions including GATA3 in four families. Sequence analysis showed heterozygous novel mutations in three families: a missense mutation within the first zinc finger domain at exon 4 (T823A, W275R), an unusual mutation at exon 4 (900insAA plus 901insCCT or C901AACCCT) resulting in a premature stop at codon 357 with loss of the second zinc finger domain, and a nonsense mutation at exon 6 (C1099T, R367X). No GATA3 abnormalities were identified in the remaining two families. The triad of HDR syndrome was variably manifested by patients with GATA3 abnormalities. The results suggest that HDR syndrome is primarily caused by GATA3 haploinsufficiency and is associated with a wide phenotypic spectrum.
authors.affiliation: Department of Paediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. komur@mx6.ttcn.ne.jp
authors.forename: K
authors.initials: K
authors.lastname: Muroya
authors.forename: T
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Nagai
authors.forename: H
authors.initials: H
authors.lastname: Isotani
authors.forename: Y
authors.initials: Y
authors.lastname: Iwata
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: S
authors.initials: S
authors.lastname: Seishu
authors.forename: Y
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D003638:Deafness / Q000175:diagnosis / Q000235:genetics*; D005192:Family Health; D005260:Female; D050990:GATA3 Transcription Factor; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007011:Hypoparathyroidism / Q000175:diagnosis / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007668:Kidney / Q000002:abnormalities*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D015534:Trans-Activators