The hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by heterozygous mutations of the GATA3 gene. In the last 20 years, since the identification of the genetic cause of the HDR syndrome, GATA3 mutations have been reported in 124 families (177 patients). The clinical aspects and molecular genetics of the HDR syndrome are reviewed here together with the reported mutations and phenotypes. Reported mutations consist of 40% frameshift deletions or insertions, 23% missense mutations, 14% nonsense mutations, 6% splice‐site mutations, 1% in‐frame deletions or insertions, 15% whole‐gene deletions, and 1% whole‐gene duplication. Missense mutations were found to cluster in the regions encoding the two GATA3 zinc‐finger domains. Patients showed great clinical variability and the penetrance of each HDR defect increased with age. The most frequently observed abnormality was deafness (93%), followed by hypoparathyroidism (87%) and renal defects (61%). The mean age of diagnosis of HDR was 15.3, 7.5, and 14.0 years, respectively. However, patients with whole‐gene deletions and protein‐truncating mutations were diagnosed earlier than patients with missense mutations.

中文翻译：

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甲状旁腺功能减退症、耳聋和肾发育不良综合征：鉴定第一个 GATA3 突变后 20 年。

甲状旁腺功能减退症、耳聋和肾发育不良 (HDR) 综合征是一种常染色体显性遗传疾病，由GATA3基因的杂合突变引起。在过去的 20 年里，自从确定 HDR 综合征的遗传原因以来，GATA3已在 124 个家庭（177 名患者）中报告了突变。本文将总结 HDR 综合征的临床方面和分子遗传学以及报告的突变和表型。报告的突变包括 40% 移码缺失或插入、23% 错义突变、14% 无义突变、6% 剪接位点突变、1% 框内缺失或插入、15% 全基因缺失和 1% 全基因复制。发现错义突变聚集在编码两个 GATA3 锌指结构域的区域。患者表现出很大的临床变异性，每个 HDR 缺陷的外显率随着年龄的增长而增加。最常观察到的异常是耳聋 (93%)，其次是甲状旁腺功能减退症 (87%) 和肾脏缺陷 (61%)。HDR 的平均诊断年龄分别为 15.3、7.5 和 14.0 岁。然而，