High-throughput Sequencing to Identify Monogenic Etiologies in a Preselected Polycystic Ovary Syndrome Cohort

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCRESPO, Raiane P.
dc.contributor.authorROCHA, Thais P.
dc.contributor.authorMONTENEGRO, Luciana R.
dc.contributor.authorNISHI, Mirian Y.
dc.contributor.authorJORGE, Alexander A. L.
dc.contributor.authorMACIEL, Gustavo A. R.
dc.contributor.authorBARACAT, Edmund
dc.contributor.authorLATRONICO, Ana Claudia
dc.contributor.authorMENDONCA, Berenice B.
dc.contributor.authorGOMES, Larissa G.
dc.date.accessioned2022-08-12T17:03:35Z
dc.date.available2022-08-12T17:03:35Z
dc.date.issued2022
dc.description.abstractContext: Polycystic ovary syndrome (PCOS) etiology remains to be elucidated, but familial clustering and twin studies have shown a strong heritable component. Objective: The purpose of this study was to identify rare genetic variants that are associated with the etiology of PCOS in a preselected cohort. Methods: This prospective study was conducted among a selected group of women with PCOS. The study's inclusion criteria were patients with PCOS diagnosed by the Rotterdam criteria with the following phenotypes: severe insulin resistance (IR), normoandrogenic-normometabolic phenotype, adrenal hyperandrogenism, primary amenorrhea, and familial PCOS. Forty-five patients were studied by target sequencing, while 8 familial cases were studied by whole exome sequencing. Results: Patients were grouped according to the inclusion criteria with the following distribution: 22 (41.5%) with severe IR, 13 (24.5%) with adrenal hyperandrogenism, 7 (13.2%) with normoandrogenic phenotype, 3 (5.7%) with primary amenorrhea, and 8 (15.1%) familial cases. DNA sequencing analysis identified 1 pathogenic variant in LMNA, 3 likely pathogenic variants in INSR, PIK3R1, and DLK1, and 6 variants of uncertain significance level with interesting biologic rationale in 5 genes (LMNA, GATA4, NR5A1, BMP15, and FSHR). LMNA was the most prevalent affected gene in this cohort (3 variants). Conclusion: Several rare variants in genes related to IR were identified in women with PCOS. Although IR is a common feature of PCOS, patients with extreme or atypical phenotype should be carefully evaluated to rule out monogenic conditions.eng
dc.description.indexPubMedeng
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2019/27631-7, 2015/17350-0]
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoas de Nivel Superior (CAPES) [2014/1459789]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [153237/2016-3]
dc.identifier.citationJOURNAL OF THE ENDOCRINE SOCIETY, v.6, n.9, 2022
dc.identifier.doi10.1210/jendso/bvac106
dc.identifier.eissn2472-1972
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/48268
dc.language.isoeng
dc.publisherENDOCRINE SOCeng
dc.relation.ispartofJournal of the Endocrine Society
dc.rightsopenAccesseng
dc.rights.holderCopyright ENDOCRINE SOCeng
dc.subjectpolycystic ovary syndromeeng
dc.subjectgeneticseng
dc.subjectinsulin resistanceeng
dc.subjecttarget sequencingeng
dc.subjectexome sequencingeng
dc.subject.othergenome-wide associationeng
dc.subject.othermutationseng
dc.subject.othervariantseng
dc.subject.othergeneeng
dc.subject.otherheritabilityeng
dc.subject.otherprevalenceeng
dc.subject.otherresistanceeng
dc.subject.otherreceptoreng
dc.subject.otherroleseng
dc.subject.otherwomeneng
dc.subject.wosEndocrinology & Metabolismeng
dc.titleHigh-throughput Sequencing to Identify Monogenic Etiologies in a Preselected Polycystic Ovary Syndrome Cohorteng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.citation.scopus3
hcfmusp.contributor.author-fmusphcRAIANE PINA CRESPO TEIXEIRA
hcfmusp.contributor.author-fmusphcTHAIS MACHADO PAGLIARO ROCHA
hcfmusp.contributor.author-fmusphcLUCIANA RIBEIRO MONTENEGRO
hcfmusp.contributor.author-fmusphcMIRIAN YUMIE NISHI
hcfmusp.contributor.author-fmusphcALEXANDER AUGUSTO DE LIMA JORGE
hcfmusp.contributor.author-fmusphcGUSTAVO ARANTES ROSA MACIEL
hcfmusp.contributor.author-fmusphcEDMUND CHADA BARACAT
hcfmusp.contributor.author-fmusphcANA CLAUDIA LATRONICO XAVIER
hcfmusp.contributor.author-fmusphcBERENICE BILHARINHO DE MENDONCA
hcfmusp.contributor.author-fmusphcLARISSA GARCIA GOMES
hcfmusp.description.issue9
hcfmusp.description.volume6
hcfmusp.origemWOS
hcfmusp.origem.pubmed35898701
hcfmusp.origem.scopus2-s2.0-85136242561
hcfmusp.origem.wosWOS:000830469400001
hcfmusp.publisher.cityWASHINGTONeng
hcfmusp.publisher.countryUSAeng
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