A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis
A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis
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DOI：
10.1093/molehr/gah216
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发表时间：
2005-11-01
影响因子：
4
通讯作者：
Méndez, JP
中科院分区：
文献类型：
--
作者：
Canto, P;Vilchis, F;Méndez, JP
混合性性腺发育不全（MGD）的病因尚未完全阐明。分子分析未能证明 Y 染色体性别决定区 (SRY) 存在突变；有人认为，这些人可能携带与睾丸决定途径有关的其他基因突变。沙漠刺猬 (DHH) 对于雄性性别分化的重要性已在我们在此描述的各种研究中得到证明，首次在两个 MGD 病例中，其中 DHH 中的单等位基因单碱基缺失与该疾病相关。从 10 名无关的 MGD 患者和 3 名对照者的石蜡包埋性腺组织中分离出基因组 DNA；此外，还提取了 100 名对照者外周血白细胞的 DNA。通过外显子特异性 PCR、单链构象多态性 (SSCP) 和直接测序评估 DHH 的编码序列异常。在两名患者中，在外显子 3 中发现了杂合 1086delG。将先前描述的 DHH 突变与本研究中观察到的突变进行比较，我们可以肯定，由于 DHH 突变导致性腺发育不全的患者的表型谱是可变的。这项研究继续证明 DHH 在哺乳动物雄性性别分化中的重要性，为 DHH 构成性腺分化的关键基因提供了更多证据。
Aetiology of mixed gonadal dysgenesis (MGD) has not been completely elucidated. Molecular analyses have failed to demonstrate the presence of mutations in sex-determining region on Y chromosome (SRY); it has been suggested that these individuals may bear mutations in other genes involved in the testis-determining pathway. Desert hedgehog's (DHH) importance regarding male sex differentiation has been demonstrated in various studies we describe here, for the first time, two cases of MGD in which a monoallelic single base deletion in DHH is associated with the disorder. Genomic DNA was isolated from paraffin-embedded gonad tissue from 10 unrelated patients with MGD and three controls; in addition to, DNA from peripheral blood leukocytes in 100 controls. Coding sequence abnormalities in DHH were assessed by exon-specific PCR, single-stranded conformation polymorphism (SSCP) and direct sequencing. In two patients, a heterozygous 1086delG in exon 3 was found. Comparing previously described mutations in DHH to the one observed in this study, we can affirm that the phenotypic spectrum of patients with gonadal dysgenesis due to mutations in DHH is variable. This study continues to demonstrate the importance that DHH has in mammalian male sexual differentiation, providing extended evidence that DHH constitutes a key gene in gonadal differentiation.