[Analysis of CHD7 gene variants in 22 patients with idiopathic hypogonadotropic hypogonadism].

OBJECTIVE

To explore clinical evaluation and genetic analysis of patients with idiopathic hypogonadotropic hypogonadism (IHH).

METHODS

The clinical data and phenotypes of 22 patients with IHH diagnosed and treated in our department were reviewed and analyzed. Whole-exome sequencing (WES) and Sanger method were used for variant analysis and verification.

RESULTS

Among the 22 cases of IHH probands, 12 cases of Kalman syndrome (KS) and 10 cases of IHH (nIHH) with normal sense of smell. On physical examination, males showed short penis, small testicles, small or inconspicuous laryngeal knots, and a sharp voice. Mammary gland development, mammary gland dysplasia, primary amenorrhea, etc. in women. Sex hormone examination: Follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) levels are reduced or at the lower limit of normal. There were nine missense variants of CHD7 gene in 8 patients. Based on the American College of Medical Genetics and Genomics guidelines, the c.307T>A(p.Ser103Thr), c.3143G>A(p.Gly1048Glu), c.6956G>T (p.Arg2319Leu) and c.3145A>T (p.Ser1049Cys) variants of CHD7 gene were predicted to be likely pathogenic (PS1+PP1+PM2, PM2+PM6+PP2+PP3, PM2+PM5+PM6+PP2+PP3 and PM2+PM6+PP2+PP3), the remaining 14 cases of IHH patients had negative genetic screening.

CONCLUSION

CHD7 gene variants may be related to IHH disease.