A novel homozygous 1-bp deletion in the NOBOX gene in two Brazilian sisters with primary ovarian failure

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art_FRANCA_A_novel_homozygous_1bp_deletion_in_the_NOBOX_2017.PDF (527.1 KB)
Citações na Scopus
17
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
SPRINGER
Autores
PITA, Carmem C.
FONTENELE, Eveline G. P.
Citação
ENDOCRINE, v.58, n.3, p.442-447, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Purpose Primary ovarian failure (POF) is characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women leading to infertility under the age of 40 years. POF is a heterogeneous disease with different causes, and several genes have been associated with the POF phenotype. Thus, Whole-exome sequencing (WES) was performed in a consanguineous family with two sisters affected by POF. Methods All exons of both sisters were massively sequenced by WES, and the segregation was confirmed by Sanger sequencing. Results The novel homozygous c.1489delT variant in the NOBOX gene was identified in the two sisters with POF. Their parents were heterozygous carriers of this variant and, therefore, consistent with an autosomal recessive mode of inheritance. The c.1489delT NOBOX variant has not been previously reported in any public available databases (1000Genomes, 6500ESP/EVS, ExAC, and gnomAD). Furthermore, this variant was neither present in 387 Brazilian exomes control individuals nor in 200 fertile Brazilian women screened by Sanger sequencing. Conclusion We report the first familial case of a novel homozygous NOBOX variant with an autosomal recessive mode of inheritance, thus allowing for a genetic diagnosis of primary ovarian failure.
Palavras-chave
NOBOX, Primary ovarian failure, Whole-exome sequencing, Homozygous variant
URI
https://observatorio.fm.usp.br/handle/OPI/24178
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/42