PT - JOURNAL ARTICLE AU - Koji Muroya AU - Tomonobu Hasegawa AU - Yoshiya Ito AU - Toshiro Nagai AU - Haruhiko Isotani AU - Yasuyoshi Iwata AU - Keiichi Yamamoto AU - Shinji Fujimoto AU - Sotofumi Seishu AU - Yoshimitsu Fukushima AU - Yukihiro Hasegawa AU - Tsutomu Ogata TI - GATA3 abnormalities and the phenotypic spectrum of HDR syndrome AID - 10.1136/jmg.38.6.374 DP - 2001 Jun 01 TA - Journal of Medical Genetics PG - 374--380 VI - 38 IP - 6 4099 - http://jmg.bmj.com/content/38/6/374.short 4100 - http://jmg.bmj.com/content/38/6/374.full SO - J Med Genet2001 Jun 01; 38 AB - 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.