Muroya K, Hasegawa T, Ito Y, Nagai T, Isotani H, Iwata Y, Yamamoto K, Fujimoto S, Seishu S, Fukushima Y, Hasegawa Y, Ogata T
Department of Paediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
J Med Genet. 2001 Jun;38(6):374-80. doi: 10.1136/jmg.38.6.374.
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.
我们报告了对9个患有HDR综合征（甲状旁腺功能减退、感音神经性耳聋和肾发育不良）（MIM 146255）的日本家族进行的GATA3分析及表型谱。荧光原位杂交和微卫星分析显示4个家族存在包括GATA3在内的杂合大片段缺失。序列分析显示3个家族存在杂合新突变：外显子4第一个锌指结构域内的错义突变（T823A，W275R）、外显子4的异常突变（900insAA加901insCCT或C901AACCCT），导致第357密码子提前终止并缺失第二个锌指结构域，以及外显子6的无义突变（C1099T，R367X）。其余2个家族未发现GATA3异常。GATA3异常的患者中，HDR综合征三联征的表现各不相同。结果表明，HDR综合征主要由GATA3单倍体不足引起，且与广泛的表型谱相关。
