GNRHR biallelic and digenic mutations in patients with normosmic congenital hypogonadotropic hypogonadism
2017; Bioscientifica; Volume: 6; Issue: 6 Linguagem: Inglês
10.1530/ec-17-0104
ISSN2049-3614
AutoresCatarina Gonçalves, José Maria Aragüés, Margarida Bastos, Luísa Barros, Nuno Vicente, Davide Carvalho, Manuel C. Lemos,
Tópico(s)Sexual Differentiation and Disorders
ResumoNormosmic 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.Cross-sectional study of 40 unrelated patients with nCHH.Patients were screened for mutations in the GNRHR gene by DNA sequencing.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.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.
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