A novel variant in LCHGR gene in 3 siblings with type 1 Leydig cell hypoplasia

Abstract

Introduction

Leydig cell hypoplasia (LCH) is an autosomal recessive disease that causes 46, XY sex development disorder. The patients with LCH are usually in the female phenotype and are presented with the complaints of no breast development and primary amenorrhea. In this article, the cases of three siblings who presented with primary amenorrhea and who had LCH were presented.

Case

A 16-year-old patient with female phenotype is presented with primary amenorrhea. Breast development was at Tanner stage 1, the external genitalia were completely in female phenotype. The karyotype was determined as 46, XY. The hormonal analyses revealed that the testosterone synthesis was insufficient despite the high level of luteinizing hormone (LH). Cortisol, ACTH, 17-Hydroxyprogesterone, and AMH levels were normal. LCH diagnosis was considered in the patient with elevated LH and no testosterone synthesis. A new mutation of homozygous c.161 + 4A > G was detected in LHCGR gene. The same mutation was detected in the patient’s two siblings with female phenotype and 46, XY karyotype.

Conclusion

In patients presenting with primary amenorrhea and karyotype 46, XY, there is no testosterone synthesis and if there is LH elevation, LCH should be considered. We found a novel variant in the LHCGR gene in three siblings with karyotype 46, XY and female phenotype.

摘要

前言： 睾丸间质细胞发育不全（LCH）是一种常染色体隐性遗传疾病, 可引起46, XY性发育障碍。LCH患者通常为女性表型, 并表现为无乳腺发育和原发性闭经。本文介绍了患有原发性闭经和诊断为LCH的三同胞病例。

病例： 一名女性表型的16岁患者出现原发性闭经。乳房发育表现Tanner 1级, 外生殖器完全处于女性表型。核型确定为46, XY。激素分析表明, 尽管黄体生成激素（LH）水平很高, 但睾酮合成不足。皮质醇, ACTH, 17-羟孕酮和AMH水平正常。LH升高且无睾酮合成的患者考虑诊断LCH。在LHCGR基因中检测到一个新的纯合c.161 + 4A> G突变。在患者的两个具有女性表型和46个XY核型的同胞中也检测到了相同的突变。

结论： 患有原发性闭经且核型为46, XY的患者没有睾酮合成时, 如果LH升高, 则应考虑LCH。我们在核型为46, XY和女性表型的三个同胞中发现了LHCGR基因的一个新变异。

Keywords:

• Primary amenorrhea
• Leydig cell hypoplasia
• LHCGR mutation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Table 1. The clinical, biochemical, and hormonal findings in the three patients.