GNRHR biallelic and digenic mutations in patients with normosmic congenital hypogonadotropic hypogonadism

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Gonçalves, CI (Author) Other; Aragüés, JM (Author) Other; Bastos, M (Author) Other; Barros, L (Author) Other; Vicente, N (Author) Other; Carvalho, Davide (Author) FMUP; Lemos, MC (Author) Other

Journal

Title: Endocrine Connections

Vol. 6

Pages: 360-366

Publisher: BioScientifica Ltd.

Indexing

Scopus - 13 Citations

Other information

Authenticus ID: P-00R-0JR

DOI: 10.1530/ec-17-0104

Abstract (EN): Objective: Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare disorder characterised by lack of pubertal development and infertility, due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH) and, unlike Kallmann syndrome, is associated with a normal sense of smell. Mutations in the GNRHR gene cause autosomal recessive nCHH. The aim of this study was to determine the prevalence of GNRHR mutations in a group of 40 patients with nCHH. Design: Cross-sectional study of 40 unrelated patients with nCHH. Methods: Patients were screened for mutations in the GNRHR gene by DNA sequencing. Results: GNRHR mutations were identified in five of 40 patients studied. Four patients had biallelic mutations (including a novel frameshift deletion p.Phe313Metfs*3, in two families) in agreement with autosomal recessive inheritance. One patient had a heterozygous GNRHR mutation associated with a heterozygous PROKR2 mutation, thus suggesting a possible role of synergistic heterozygosity in the pathogenesis of the disorder. Conclusions: This study further expands the spectrum of known genetic defects associated with nCHH. Although GNRHR mutations are usually biallelic and inherited in an autosomal recessive manner, the presence of a monoallelic mutation in a patient should raise the possibility of a digenic/oligogenic cause of nCHH. © 2017 The authors Published by Bioscientifica Ltd.

Language: English

Type (Professor's evaluation): Scientific