| Full text | |
| Author(s): |
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.
Total Authors: 9
|
| Document type: | Journal article |
| Source: | SEXUAL DEVELOPMENT; v. 11, n. 3, p. 137-142, 2017. |
| Web of Science Citations: | 8 |
| Abstract | |
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) | |
| FAPESP's process: | 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine |
| Grantee: | Berenice Bilharinho de Mendonça |
| Support Opportunities: | Research Projects - Thematic Grants |