GATA3 abnormalities and the phenotypic spectrum of HDR syndrome
- Koji Muroyaa,b,
- Tomonobu Hasegawaa,
- Yoshiya Itoc,
- Toshiro Nagaid,
- Haruhiko Isotanie,
- Yasuyoshi Iwataf,
- Keiichi Yamamotoa,
- Shinji Fujimotog,
- Sotofumi Seishuh,
- Yoshimitsu Fukushimai,
- Yukihiro Hasegawaj,
- Tsutomu Ogataa,b
- aDepartment of Paediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan, bDepartment of Paediatrics, Tokyo Electric Power Company Hospital, Tokyo, Japan, cDepartment of Paediatrics, Asahikawa Medical College, Asahikawa, Japan, dDepartment of Paediatrics, Dokkyo University School of Medicine, Koshigaya Hospital, Koshigaya, Japan, eDepartment of Internal Medicine, Hirakata City Hospital, Hirakata, Japan, fDepartment of Internal Medicine, Kurashiki Chuo Hospital, Kurashiki, Japan, gDepartment of Paediatrics, Nagoya City University Medical School, Nagoya, Japan, hDepartment of Paediatrics, Noto General Hospital, Nanao, Japan, iDepartment of Hygiene and Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan, jEndocrinology, Metabolism, and Genetics Unit, Tokyo Metropolitan Kiyose Children's Hospital,Kiyose, Japan
- Dr Muroya,komur{at}mx6.ttcn.ne.jp
- Revised 28 February 2001
- Accepted 1 March 2001
Abstract
We report on GATA3 analysis and the phenotypic spectrum in nine Japanese families with the HDR syndrome (hypoparathyroidism, sensorineuraldeafness, andrenal 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.
