A case report of congenital idiopathic hypogonadotropic hypogonadism caused by novel mutation of GNRHR gene. Issue 5 (5th February 2021)

• Record Type: Journal Article
• Authors: Wang, Liping; Lin, Weisheng; Li, Xiaohong; Zhang, Lijuan; Wang, Kai; Cui, Xiaoli; Tang, Shanmei; Fang, Guangguang; Tan, Yan; Wang, Xuelai; Chen, Chuan; Yang, Chuanchun; Tang, Huiru
• Other Names: Saranathan. Maya section editor.
• Is Part Of: Medicine. Volume 100:Issue 5(2021)
• Publication Date: 2021-02-05
• Subjects: congenital idiopathic hypogonadotropic hypogonadism -- GNRHR -- missense mutation -- novel mutation; Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000024007
• Languages: English
• ISSNs: 0025-7974

Abstract

Abstract: Rationale: This 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 concerns: A 23-year-old girl presented with primary amenorrhea, sparse pubic hair, lack of breast development, and delayed sexual development. Diagnoses: Combined with the clinical characteristics, auxiliary examinations, and molecular genetic analysis, the patient was diagnosed as IHH. Interventions: Whole exome and Sanger sequencing were performed to validate the mutation in family members. Outcomes: A 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. Lessons: We 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.