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Type: Artigo
Title: New genetic findings in a large cohort of congenital hypogonadotropic hypogonadism
Author: Amato, Lorena Guimaraes Lima
Montenegro, Luciana Ribeiro
Lerario, Antonio Marcondes
Jorge, Alexander Augusto Lima
Guerra Junior, Gil
Schnoll, Caroline
Renck, Alessandra Covallero
Trarbach, Ericka Barbosa
Costa, Elaine Maria Frade
Mendonca, Berenice Bilharinho
Latronico, Ana Claudia
Silveira, Leticia Ferreira Gontijo
Abstract: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by GnRH deficiency. Several genes have been associated with the pathogenesis of CHH, but most cases still remain without a molecular diagnosis. The advent of next-generation sequencing (NGS) has allowed the simultaneous genotyping of several regions, faster, making possible the extension of the genetic knowledge of CHH. Objective: Genetic characterization of a large cohort of Brazilian CHH patients. Design and patients: A cohort of 130 unrelated patients (91 males, 39 females) with CHH (75 normosmic CHH, 55 Kallmann syndrome) was studied using a panel containing 36 CHH-associated genes. Results: Potential pathogenic or probably pathogenic variants were identified in 43 (33%) CHH patients. The genes ANOS1, FGFR1 and GNRHR were the most frequently affected. A novel homozygous splice site mutation was identified in the GNRH1 gene and a deletion of the entire coding sequence was identified in SOX10. Deleterious variants in the IGSF10 gene were identified in two patients with reversible normosmic CHH. Notably, 6.9% of the patients had rare variants in more than one gene. Rare variants were also identified in SPRY4, IL17RD, FGF17, IGSF1 and FLRT3 genes. Conclusions: This is a large study of the molecular genetics of CHH providing new genetic findings for this complex and heterogeneous genetic condition. NGS has been shown to be a fast, reliable and effective tool in the molecular diagnosis of congenital CHH and being able to targeting clinical genetic testing in the future
Subject: Hipogonadismo
Country: Reino Unido
Editor: BioScientifica
Rights: Fechado
Identifier DOI: 10.1530/EJE-18-0764
Date Issue: 2019
Appears in Collections:FCM - Artigos e Outros Documentos

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