LHCGR基因突变所致家族性男性限性性早熟家系分析暨文献复习

Family analysis of familial male precocious puberty caused by LHCGR gene mutation and literature review

目的 报道1例家族性男性限性性早熟(FMPP)病儿及家族的临床特征及基因分析。方法 回顾性收集2022年4月就诊于徐州医科大学附属徐州儿童医院的1例3岁2个月FMPP病儿的临床资料,包括体格检查、实验室相结果等,并测序病儿及其父母外周血LHCGR基因的11个外显子编码区。结果 病儿自生后2个月起出现外生殖器阴茎增大,身高增长加速,现身高110.5 cm,双侧睾丸4 mL,阴茎长6.3 cm、横径3.5 cm,阴毛2期;血睾酮8.09 nmol/L,促性腺激素释放激素(GnRH)激发试验呈青春期前低水平表现;LHCGR基因的11号c.1118C>T,导致373位丙氨酸变为缬氨酸。病儿母亲检测到相同的基因突变位点,有多囊卵巢病史。结论 FMPP是外周性性早熟罕见病因,该病例临床表现典型,检测发现LHCGR基因杂合突变c.1118C>T(p.Ala 373 Val),母子具有相同基因型但表型不同,母亲为多囊卵巢病人,为该文献复习FMPP病因诊断、产前诊断及家系的遗传咨询提供依据。

Objective To report the clinical characteristics and genetic analysis of a child with familial male-limited precocious puberty(FMPP) and the family.Methods The clinical data of a 3-year and 2-month-old child with FMPP who was admitted to Xuzhou Children's Hospital Affiliated to Xuzhou Medical University in April 2022 were retrospectively collected,including physical examination and laboratory test results,and the 11 exon coding regions of the LHCGR gene in the peripheral blood of the child and his parents were sequenced.Results The external genitals and penis were enlarged 2 months after birth,and the growth accelerated after birth.The present height was 110.5 cm,bilateral testicles 4 mL,penis length 6.3 cm,transverse diameter 3.5 cm,pubic hair stage 2;serum testosterone was 8.09 nmol/L;Gonadotropin releasing hormone(GnRH) stimulation test showed low levels of prepubertal performance.No.11 c.1118C>T of the LHCGR gene resulted in the change of alanine at position 373 to valine.The same gene mutation site was detected in the mother of the child with a history of polycystic ovary.Conclusions FMPP is a rare cause of peripheral precocious puberty.The typical clinical manifestations of this case is heterozygous mutation of LHCGR gene C.1118C>T(P.Ala 373 Val).The mother and child have the same genotype but different phenotype,and the mother is a patient with polycystic ovary,which provid basis for etiological diagnosis,prenatal diagnosis and genetic counseling of FMPP in this literature review.