新的LH受体突变致Leydig细胞发育不全的家系研究

Study on a pedigree with Leydig cell hypoplasia caused by novel mutation of luteinizing hormone receptor

目的本研究通过对一中国人的Leydig细胞发育不全（LCH）家系的临床诊断及基因检测，探讨其病理生理特点。方法总结分析临床资料，通过激素测定以及青春期前后人绒毛膜促性腺激素（hCG）兴奋试验确认其临床诊断；并用PCR产物直接测序的方法检测患者及其家系成员的LH／hCG受体（LHCGR）基因。结果表现为男性假两性畸形的患者睾酮水平低下，且不能被hCG兴奋，青春期后出现LH水平的显著升高。DNA序列分析发现患者的LHCGR基因有两种新的突变，一等位基因含有第5号外显子T—C的杂合点突变，使受体胞外域的152位的异亮氨酸突变为苏氨酸；另一等位基因存在第6号内含子3’端的剪切位点C突变为A（IVS6—3C→A）。患者无临床表现的同胞妹妹（46，XX）具有和患者相同的基因型。结论患者LCH由LHCGR基因新的复合杂合突变所致。

Objective To investigate a Chinese pedigree suffering from Leydig cell hypoplasia （LCH） based on clinical data and genetic diagnosis. Methods The patient was diagnosed by means of clinical data, hormone profiles, and human chorionic gonadotropin （ hCG ） test. The luteinizing hormone/ehorionie gonadotropin receptor（LHCGR） gene of the patient and family members was amplified and sequenced. Results The patient presented with male pseudohermaphroditism, low level of testosterone, which did not respond to hCG. Genetic analysis of the LHCGR revealed two novel mutations ： a missense mutation located in exon 5, resulting in Ile replaced by Thr in the extracellular domain; and a splice site mutation in the 3＇ terminal of intron 6 （ IVS6-3 C→A）. Proband＇s sister （46, XX）who lacked clinical manifestations showed the identical genotype with the patient. Conclusions A mutation in the consensus sequence of 3＇ splice site, in addition to a missense mutation （Ile152Thr） in the extracellular ligand-binding domain is the cause of inactivation of the LHCGR gene in patient with Leydig cell hypoplasia.