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01-12-2017 | Endocrine Genetics/Epigenetics

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

Authors: Monica M. França, Mariana F. A. Funari, Antonio M. Lerario, Mirian Y. Nishi, Carmem C. Pita, Eveline G. P. Fontenele, Berenice B. Mendonca

Published in: Endocrine | Issue 3/2017

Abstract

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.

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Title: A novel homozygous 1-bp deletion in the NOBOX gene in two Brazilian sisters with primary ovarian failure
Authors: Monica M. França
Mariana F. A. Funari
Antonio M. Lerario
Mirian Y. Nishi
Carmem C. Pita
Eveline G. P. Fontenele
Berenice B. Mendonca
Publication date: 01-12-2017
Publisher: Springer US
Published in: Endocrine / Issue 3/2017
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-017-1459-2

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

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Purpose

Methods

Results

Conclusion

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