LHCGR基因突变（Asp578His）致家族性男性性早熟1例临床特点及基因分析

Familial male-limited precocious puberty due to Asp578His mutations in the LHCGR gene:clinical characteristics and gene analysis in an infant

摘要:

该文报道1例由LHCGR基因激活性杂合突变导致的家族性男性性早熟（FMPP）患儿的临床特点及基因分析。患儿为男性，婴儿时期出现了外生殖器增长过快、生长加速，伴阴毛及阴茎勃起，结合患儿性征检查、促性腺激素释放激素兴奋试验、血清睾酮检测及骨龄检查等结果，临床诊断为外周性性早熟。随后对患儿及其父母的性早熟相关基因进行检测。基因测序结果提示患儿黄体生成素/绒毛膜促性腺激素受体（LHCGR）基因第11外显子1732G > C突变，导致578位氨基酸由天冬氨酸变为组氨酸，该突变是1个未见文献报道的新突变，且父母基因检测结果未见异常。联用第3代芳香化酶抑制剂来曲唑和抗雄激素制剂螺内酯治疗半年后，患儿症状得到控制。该研究结果扩展了LHCGR基因突变谱，为FMPP病因诊断及家系的遗传咨询和产前诊断提供了分子依据。

Abstract:

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.