| Full text | |
| Author(s): |
Franca, Monica M.
[1]
;
Funari, Mariana F. A.
[1]
;
Lerario, Antonio M.
[1, 2, 3]
;
Nishi, Mirian Y.
[1, 2]
;
Pita, Carmem C.
[1]
;
Fontenele, Eveline G. P.
[4]
;
Mendonca, Berenice B.
[1, 2]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Unidade Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol LIM42, Hosp Clin, Disciplina Endocrinol, Fac Med, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Lab Sequenciamento Larga Escala SELA, Sao Paulo - Brazil
[3] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA
[4] Univ Fed Ceara, Hosp Univ Walter Cantidio, Ser Endocrinol & Diabet, Fortaleza, Ceara - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | ENDOCRINE; v. 58, n. 3, p. 442-447, DEC 2017. |
| Web of Science Citations: | 3 |
| 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. (AU) | |
| FAPESP's process: | 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine |
| Grantee: | Berenice Bilharinho de Mendonça |
| Support Opportunities: | Research Projects - Thematic Grants |