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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.)

A Novel Homozygous Missense FSHR Variant Associated with Hypergonadotropic Hypogonadism in Two Siblings from a Brazilian Family

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Autor(es):
Franca, Monica M. ; Lerario, Antonio M. ; Funari, Mariana F. A. ; Nishi, Mirian Y. ; Narcizo, Amanda M. ; de Mello, Maricilda P. ; Guerra-Junior, Gil ; Maciel-Guerra, Andrea T. ; Mendonca, Berenice B.
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: SEXUAL DEVELOPMENT; v. 11, n. 3, p. 137-142, 2017.
Citações Web of Science: 8
Resumo

Hypergonadotropic hypogonadism (HH) is defined by increased gonadotropin levels in men and women. Primary ovarian failure (POF) is a form of female infertility characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women under the age of 40 years. Although several genes have been associated with POF, its causative genes remain to be identified. Here, we used whole-exome sequencing (WES) to study a consanguineous family with a 46, XX girl and a 46, XY man affected by HH. All exons of both siblings and their parents were captured and massively sequenced by WES, and the candidate variant was confirmed by Sanger sequencing. A novel c. 1298C> A; p. Ala433Asp missense variant of the follicle-stimulating hormone receptor (FSHR) gene was found in both affected siblings in a homozygous state and in their parents in a heterozygous state. This FSHR variant is not present in available databases (1000 Genomes and NHLBI/ EVS) and Brazilian exome controls.Moreover, it is highly conserved and predicted as deleteriousin all prediction sites analyzed. In conclusion, the novel homozygousFSHR variant observed in 2 siblings with HH canexpand the spectrum of FSHR mutations in humans. (C) 2017 S. Karger AG, Basel (AU)

Processo FAPESP: 13/02162-8 - Patogênese molecular e caracterização de doenças monogênicas do desenvolvimento: um caminho para a medicina translacional
Beneficiário:Berenice Bilharinho de Mendonça
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 14/50137-5 - Caracterização molecular de doenças monogênicas do desenvolvimento por sequenciamento em larga escala
Beneficiário:Berenice Bilharinho de Mendonça
Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários