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

作者：Franca Monica M; Funari Mariana F A; Lerario Antonio M; Nishi Mirian Y; Pita Carmem C; Fontenele Eveline G P; Mendonca Berenice B^*

来源：Endocrine, 2017, 58(3): 442-447.

DOI：10.1007/s12020-017-1459-2

• NOBOX
• Primary ovarian failure
• Whole-exome sequencing
• Homozygous variant

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.

• 出版日期2017-12