先天性肾上腺发育不良伴低促性腺激素性性腺功能不全患者的临床及分子遗传学研究  

Clinical and molecular genetic analysis of a patient with adrenal hypoplasia congenital and hypogonadotropic hypogonadism

作　　者：张化冰[1] 聂敏[1] 

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院内分泌科,卫生部内分泌重点实验室

出　　处：《生殖医学杂志》2011年第3期183-187,共5页Journal of Reproductive Medicine

基　　金：国家自然科学基金项目(30672210:81070630)

摘　　要：目的探讨1例X连锁的先天性肾上腺发育不良(AHC)伴低促性腺激素性性功能不全患者的临床表现及其分子生物学基础。方法详细收集患者的临床资料、生化检查及影像学检查结果,抽取外周静脉血,提取基因组DNA,聚合酶链反应(PCR)扩增DAX-1基因的2个外显子及其与内含子的边界,测序确定突变情况。结果患者临床表现、实验室检查和影像学检查符合AHC诊断。基因突变分析显示,患者的DAX-1基因第一外显子发生插入突变,为c.990insG,造成第331位氨基酸由天门冬酰胺改变为谷氨酰胺及此后的氨基酸移码突变,并在57个氨基酸之后提前终止(p.Asn331GlnfsX58)。结论通过DAX-1基因突变分析,从分子遗传学方面证实患者的诊断。临床上存在低促性腺激素性性腺功能不全(HH)和(或)原发性肾上腺皮质功能不全表现的患者应该考虑到该疾病可能,基因分析有助于确诊。Objective： To analyze the clinical manifestations and molecular basis of X-linked adrenal hypoplasia congenital （AHC） accompanied by hypogonadotropic hypogonadism （HH）. Methods： Clinical features and laboratory data were collected from the patient with AHC and HH. Genomic DNA was extracted from leukocytes of peripheral blood of the patient. Two exons of the DAX-1 gene, including the flanking regions of introns, were amplified by polymerase chain reaction （PCR）. The mutations of DAX-1 gene were identified by direct sequencing. Results： AHC was diagnosed by comprehensive consideration of the clinical presentations and the lab tests. Gene mutation test revealed an insertion mutation in the first exon of DAX-1 gene （c. 990insG）, which caused a missense mutation of Asn to Gln at codon 331 and the open reading frame shift following this codon to produce a truncated enzyme with 388 amino acids （p. Asn331GlnfsX58）. Conclusions. With DAX-1 gene mutation analysis, the diagnosis of AHC was confirmed in the patient. This case demonstrates that it is important to be aware of HH being the presenting feature of AHC, and the mutational analysis of DAX-1 being helpful to the diagnosis.

关 键 词：X连锁的先天性肾上腺发育不良 DAX-1基因 基因突变 原发性肾上腺皮质功能不全 低促性腺激 素性性腺功能不全 

分 类 号：R[医药卫生]