| Full text | |
| Author(s): Show less - |
Franca, Monica M.
[1, 2]
;
Funari, Mariana F. A.
[1]
;
Lerario, Antonio M.
[3]
;
Santos, Mariza G.
[1]
;
Nishi, Mirian Y.
[1, 4]
;
Domenice, Sorahia
[1]
;
Moraes, Daniela R.
[1]
;
Costalonga, Everlayny F.
[5]
;
Maciel, Gustavo A. R.
[6]
;
Maciel-Guerra, Andrea T.
[7]
;
Guerra-Junior, Gil
[8]
;
Mendonca, Berenice B.
[1, 4]
Total Authors: 12
|
| Affiliation: | [1] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Unidade Endocrinol Desenvolvimento, Lab Hormonios, Sao Paulo, SP - Brazil
[2] Univ Chicago, Dept Med, Sect Endocrinol, 5841 S Maryland Ave, Chicago, IL 60637 - USA
[3] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA
[4] Univ Sao Paulo FMUSP, Lab Sequenciamento Larga Escala SELA, Fac Med, Sao Paulo, SP - Brazil
[5] Univ Fed Espirito Santo, Dept Clin Med, Fac Med, Vitoria, ES - Brazil
[6] Univ Sao Paulo, Dept Obstet & Ginecol, Fac Med, Disciplina Ginecol, Hosp Clin HCFMUSP, Sao Paulo, SP - Brazil
[7] Univ Estadual Campinas, Fac Ciencias Med, Dept Genet Med & Med Genom, Campinas, SP - Brazil
[8] Univ Estadual Campinas, Fac Ciencias Med, Dept Pediat, Campinas, SP - Brazil
Total Affiliations: 8
|
| Document type: | Journal article |
| Source: | PLoS One; v. 15, n. 10 OCT 23 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
Primary ovarian insufficiency (POI) is a heterogeneous disorder associated with several genes. The majority of cases are still unsolved. Our aim was to identify the molecular diagnosis of a Brazilian cohort with POI. Genetic analysis was performed using a customized panel of targeted massively parallel sequencing (TMPS) and the candidate variants were confirmed by Sanger sequencing. Additional copy number variation (CNV) analysis of TMPS samples was performed by CONTRA. Fifty women with POI (29 primary amenorrhea and 21 secondary amenorrhea) of unknown molecular diagnosis were included in this study, which was conducted in a tertiary referral center of clinical endocrinology. A genetic defect was obtained in 70% women with POI using the customized TMPS panel. Twenty-four pathogenic variants and two CNVs were found in 48% of POI women. Of these variants, 16 genes were identified as BMP8B, CPEB1, INSL3, MCM9, GDF9, UBR2, ATM, STAG3, BMP15, BMPR2, DAZL, PRDM1, FSHR, EIF4ENIF1, NOBOX, and GATA4. Moreover, a microdeletion and microduplication in the CPEB1 and SYCE1 genes, respectively, were also identified in two distinct patients. The genetic analysis of eleven patients was classified as variants of uncertain clinical significance whereas this group of patients harbored at least two variants in different genes. Thirteen patients had benign or no rare variants, and therefore the genetic etiology remained unclear. In conclusion, next-generation sequencing (NGS) is a highly effective approach to identify the genetic diagnoses of heterogenous disorders, such as POI. A molecular etiology allowed us to improve the disease knowledge, guide decisions about prevention or treatment, and allow familial counseling avoiding future comorbidities. (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 |