Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPFRANCA, Monica M.FUNARI, Mariana F. A.LERARIO, Antonio M.NISHI, Mirian Y.PITA, Carmem C.FONTENELE, Eveline G. P.MENDONCA, Berenice B.2017-12-122017-12-122017ENDOCRINE, v.58, n.3, p.442-447, 20171355-008Xhttps://observatorio.fm.usp.br/handle/OPI/24178Purpose 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.engrestrictedAccessNOBOXPrimary ovarian failureWhole-exome sequencingHomozygous variantsteroidogenic factor-iinsufficiencyexpressionvariantsmutationhumanscohortarticleCopyright SPRINGER10.1007/s12020-017-1459-2Endocrinology & Metabolism1559-0100