A Novel Homozygous Missense FSHR Variant Associated with Hypergonadotropic Hypogonadism in Two Siblings from a Brazilian Family.
Sex Dev
; 11(3): 137-142, 2017.
Article
em En
| MEDLINE
| ID: mdl-28591755
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 deleterious in all prediction sites analyzed. In conclusion, the novel homozygous FSHR variant observed in 2 siblings with HH can expand the spectrum of FSHR mutations in humans.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Receptores do FSH
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Mutação de Sentido Incorreto
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Irmãos
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Hipogonadismo
Tipo de estudo:
Risk_factors_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
País como assunto:
America do sul
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Brasil
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article