Mutation analysis of NR5A1 gene in children with idiopathic hypogonadotropic hypogonadism

Abstract

Objective To study the NR5A1 gene mutation in patients with idiopathic hypogonadotropic hypogonadism(IHH), and to find the new mutation point. Methods Sixty-one IHH patients and 100 normal control subjects were collected and genomic DNA was extracted from blood samples. These patients were with normal karyotype and no abnormality was discovered in magnetic resonance imaging(MRI)scan of the pituitary. Other endocrine diseases were also excluded. The 2-7 exons and splice-sites of NR5A1 gene were amplified with polymerase chain reaction. DNA of the coding sequence and splice-sites of NR5A1 were sequenced by double deoxidizing terminal end sequencing method in 61 IHH and 100 normal control subjects. The results of sequencing were compared with their corresponding sequence data. 61 IHH kindreds were investigated and the clinical data of these patients were collected. Finally, the phenotype and genotype positive cases were analyzed. Results Six patients carried NR5A1 gene mutational sites in 61 cases of IHH. Analysis of sequencing results from 100 age and ethnicity matched control subjects did not show any of these novel changes. Conclusions One mutation in NR5A1 gene may affect protein structure and function, which should be considered in male IHH patients with normal karyotype and without insufficiency of adrenal function. (Chin J Endocrinol Metab, 2015, 31: 956-960) Key words: Idiopathic hypogonadotropic hypogonadism; NR5A1; Gene mutation