Purpose

Leydig cell hypoplasia is a rare autosomal recessive 46,XY disorder of sexual development (DSD). It is caused by homozygous or compound heterozygous inactivating mutations in the human luteinizing hormone/chorionic gonadotropin hormone receptor (LHCGR) gene. In Leydig cell hypoplasia type I, patients are characterized by predominantly female external genitalia, which usually go unrecognized until the age of puberty.

Methods

This study reports three patients descending from two unrelated families. We performed clinical, hormonal, histopathological, molecular, and bioinformatics studies for the studied cases.

Results

All investigations suggested 46,XY DSD and Leydig cell hypoplasia. Molecular analysis showed two novel homozygous inactivating mutations (p.Glu148Ter and p.Leu104Pro) within the extracellular domain of the LHCGR gene.

Conclusion

Although the mutations of the LHCGR gene are distributed heterogeneously, without hotspot or recurrent mutations, about one fifth of the reported mutations worldwide have been detected in Arab patients. This is probably due to the high consanguinity rate in these populations, which increases the percentage of autosomal recessive disorders and the homozygous LHCGR gene mutations.

中文翻译：

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LHCGR 基因在两个 46,XY DSD 家族中的新突变导致 Leydig 细胞发育不全 I。

目的

Leydig 细胞发育不全是一种罕见的常染色体隐性遗传 46,XY 性发育障碍 (DSD)。它是由人类促黄体激素/绒毛膜促性腺激素受体 (LHCGR) 基因中的纯合子或复合杂合子失活突变引起的。在 I 型间质细胞发育不全中，患者的主要特征是女性外生殖器，通常直到青春期才被发现。

方法

该研究报告了来自两个无关家庭的三名患者。我们对所研究的病例进行了临床、激素、组织病理学、分子和生物信息学研究。

结果

所有调查均提示 46,XY DSD 和 Leydig 细胞发育不全。分子分析显示 LHCGR 基因的胞外域内有两个新的纯合失活突变（p.Glu148Ter 和 p.Leu104Pro）。

结论

尽管 LHCGR 基因的突变分布不均，没有热点或复发性突变，但全世界报告的突变中约有五分之一是在阿拉伯患者中检测到的。这可能是由于这些人群的近亲率高，这增加了常染色体隐性遗传疾病和纯合 LHCGR 基因突变的百分比。