• Liping Wang, Weisheng Lin, Xiaohong Li, Lijuan Zhang, Kai Wang, Xiaoli Cui, Shanmei Tang, Guangguang Fang, Yan Tan, Xuelai Wang, Chuan Chen, Chuanchun Yang, and Huiru Tang.
• Peking University Shenzhen Hospital.
• Medicine (Baltimore). 2021 Feb 5; 100 (5): e24007e24007.

RationaleThis study aimed to investigate the genetic mutation characteristics of congenital idiopathic hypogonadotropic hypogonadism (IHH) through the clinical features and genetic analysis of 2 patients with IHH in 1 pedigree.Patient ConcernsA 23-year-old girl presented with primary amenorrhea, sparse pubic hair, lack of breast development, and delayed sexual development.DiagnosesCombined with the clinical characteristics, auxiliary examinations, and molecular genetic analysis, the patient was diagnosed as IHH.InterventionsWhole exome and Sanger sequencing were performed to validate the mutation in family members.OutcomesA novel homozygous missense mutation c.521A > G (p.Q174R) in the GNRHR gene was identified in the 2 affected sisters. Familial segregation showed that the homozygous variant was inherited from their parents respectively and the eldest sister was the carrier without correlative symptom.LessonsWe reported a novel GNRHR mutation in a pedigree with congenital idiopathic hypogonadotropic hypogonadism. Glutamine at amino acid position 174 was highly conserved among various species. The molecular structure of GNRHR protein showed that p.Q174R mutation brought in a new stable hydrogen bond between position 174 and 215, may impede conformational mobility of the TMD4 and TMD5. It suggests that the missense mutation c.521A > G related to congenital idiopathic hypogonadotropic hypogonadism was probably a causative factor for both sisters. Through high-throughput sequencing and experimental verification, we had basically determined the patient's pathogenic mutation and inheritance, which could better guide doctors for treatment.Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

23 keywords...

hide…