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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

New genetic findings in a large cohort of congenital hypogonadotropic hypogonadism

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Autor(es):
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Lima Amato, Lorena Guimaraes [1] ; Montenegro, Luciana Ribeiro [1] ; Lerario, Antonio Marcondes [2, 1] ; Lima Jorge, Alexander Augusto [3] ; Guerra Junior, Gil [4] ; Schnoll, Caroline [1] ; Renck, Alessandra Covallero [1] ; Trarbach, Ericka Barbosa [3] ; Frade Costa, Elaine Maria [1] ; Mendonca, Berenice Bilharinho [1] ; Latronico, Ana Claudia [1] ; Gontijo Silveira, Leticia Ferreira [1, 5]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Unidade Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol LIM42, Disdplina Endocrinol & Metabol, Hosp Clin, Fac Med, Sao Paulo, SP - Brazil
[2] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA
[3] Univ Sao Paulo, Unidade Endocrinol Genet LIM25, Disciplina Endocrinol & Metabol, Hosp Clin, Fac Med, Sao Paulo, SP - Brazil
[4] Univ Estadual Campinas, UNICAMP, Fac Ciencias Med, Dept Pediat, Campinas, SP - Brazil
[5] Univ Fed Minas Gerais, Fac Med, Dept Clin Med, Belo Horizonte, MG - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 181, n. 2, p. 103-119, AUG 2019.
Citações Web of Science: 2
Resumo

Context: 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. (AU)

Processo FAPESP: 14/50137-5 - Caracterização molecular de doenças monogênicas do desenvolvimento por sequenciamento em larga escala
Beneficiário:Berenice Bilharinho de Mendonça
Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
Processo FAPESP: 13/03236-5 - Novas abordagens e metodologias na investigação genético-molecular dos distúrbios de crescimento e desenvolvimento puberal
Beneficiário:Alexander Augusto de Lima Jorge
Linha de fomento: Auxílio à Pesquisa - Temático