Wang Min, Li Min, Liu Yue-Sheng, Lei Si-Min, Xiao Yan-Feng
Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2017 Nov;19(11):1159-1164. doi: 10.7499/j.issn.1008-8830.2017.11.007.
The aim of the study was to provide a descriptive analysis of familial male-limited precocious puberty (FMPP), which is a rare inherited disease caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR). The patient was a ten-month-old boy, presenting with penile enlargement, pubic hair formation, and spontaneous erections. Based on the clinical manifestations and laboratory data, including sexual characteristics, serum testosterone levels, GnRH stimulation test, and bone age, this boy was diagnosed with peripheral precocious puberty. Subsequently the precocious puberty-related genes were analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. Genetic analysis revealed a novel heterozygous missense mutation c.1732G>C (Asp578His) of the LHCGR gene exon11 in the patient, which had never been reported. His parents had no mutations. After combined treatment with aromatase inhibitor letrozole and anti-androgen spironolactone for six months, the patient's symptoms were controlled. The findings in this study expand the mutation spectrum of the LHCGR gene, and provide molecular evidence for the etiologic diagnosis as well as for the genetic counseling and prenatal diagnosis in the family.
本研究的目的是对家族性男性限性性早熟(FMPP)进行描述性分析,这是一种由促黄体生成素/绒毛膜促性腺激素受体基因(LHCGR)的杂合性组成型激活突变引起的罕见遗传病。该患者为一名10个月大的男孩,表现为阴茎增大、阴毛形成和自发性勃起。根据临床表现和实验室数据,包括性征、血清睾酮水平、GnRH刺激试验和骨龄,该男孩被诊断为外周性早熟。随后,通过对患者及其父母的扩增PCR产物进行直接DNA测序,分析了与性早熟相关的基因。基因分析发现患者LHCGR基因外显子11存在一个新的杂合错义突变c.1732G>C(Asp578His),此前未见报道。其父母无突变。在联合使用芳香化酶抑制剂来曲唑和抗雄激素螺内酯治疗6个月后,患者症状得到控制。本研究结果扩展了LHCGR基因的突变谱,为该家族的病因诊断、遗传咨询和产前诊断提供了分子证据。