Repository logo
 
Publication

Relevance of Multigene Panels in the Molecular diagnosis of patients with disorders of sexual development

2023-11Conference object Restricted access
Simple item page
dc.contributor.authorPereira-Caetano, Iris
dc.contributor.authorMendonça, Joana
dc.contributor.authorMirante, Alice
dc.contributor.authorCardoso, Rita
dc.contributor.authorRodrigues, Márcia
dc.contributor.authorOliveira, João Paulo
dc.contributor.authorGrangeia, Ana
dc.contributor.authorBarbosa, David
dc.contributor.authorVieira, Luís
dc.contributor.authorGonçalves, João
dc.date.accessioned2024-02-27T17:39:39Z
dc.date.embargo2027-12
dc.date.issued2023-11
dc.description.abstractIntroduction: Next generation sequencing (NGS) is increasingly used in the molecular diagnosis of rare diseases, such as disorders of sexual development (DSD), allowing the analysis of a greater number of genes in a single assay, providing faster results with reduced costs. DSD patients may present high phenotypic overlap (genital ambiguity, sex reversal, delayed/absent puberty, infertility) posing challenges to clinical diagnosis. NGS technology using multigene panels has higher hypothesis to identify the genetic cause and novel genetic variants in a large number of cases. Methodology: 33 genomic DNA samples from DSD patients were sequenced on MiSeq using the Ampliseq technology (Illumina). A customized gene panel covering 40 genes was used to prepare the libraries of the target sequences. The 40 genes were subdivided into 5 subpanels: primary sex determination, sex differentiation, hypogonadotropic hypogonadism/infertility, steroidogenesis and premature ovarian insufficiency. Variant classification, according to ACMG-AMP, was based on bioinformatics tools (ex. VEP, HSF, VarSome, Alamut) and databases (gnomAD, HGMD, ClinVar, dbSNP). Pathogenic, Likely pathogenic and VUS variants were confirmed by Sanger sequencing. Results: 16 of the 33 patients were previously studied in our laboratory with negative results for the main genes associated with DSD (SRY, AR, ANOS1, GNRHR, CYP21A2). We identified 9 causative variants (8P/1LP) in 7 patients (21.2%) in AR, HSD17B3, LHCGR, FGFR1 and NR5A1. One patient was a compound heterozygous for HSD17B3 and another simultaneously homozygous for LHCGR and hemizygous for AR. The remaining 5 were homozigous, heterozigous or hemizygous for HSD17B3, LHCGR, NR5A1, FGFR1 or AR. One VUS, FGFR1:c.566G>A p.Arg189His, requires familial studies to revaluate its pathogenicity. Discussion: Multigene NGS studies allows to increase the rate of variant detection, mainly in genes not included in a first molecular approach. It also contributes to establishing or confirming the clinical diagnosis, assisting in decisions regarding the treatment and reproductive management of patients and families, as well as in genetic counselling.pt_PT
dc.description.sponsorshipFCT/MCTES, Projects - ToxOmics and Human Health (UIDB/00009/2020) and GenomePT (POCI-01-0145-FEDER-022184)pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/9154
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationCentre for Toxicogenomics and Human Health
dc.relationNational Facility for genome sequencing and analysis
dc.subjectDsorders of Sexual Developmentpt_PT
dc.subjectDSDpt_PT
dc.subjectSRYpt_PT
dc.subjectSexualpt_PT
dc.subjectSex Determinationpt_PT
dc.subjectMolecular Diagnosispt_PT
dc.subjectDoenças Genéticas
dc.titleRelevance of Multigene Panels in the Molecular diagnosis of patients with disorders of sexual developmentpt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardTitleCentre for Toxicogenomics and Human Health
oaire.awardTitleNational Facility for genome sequencing and analysis
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00009%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9444 - RNIIIE/PINFRA%2F22184%2F2016/PT
oaire.citation.conferencePlaceLisboa, Portugalpt_PT
oaire.citation.title27th Annual Meeting SGH, 23-25 novembro 2023pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream9444 - RNIIIE
person.familyNameGonçalves
person.givenNameJoão
person.identifier.ciencia-id5710-1FAE-5FAB
person.identifier.orcid0000-0001-9359-8774
person.identifier.ridL-2265-2014
person.identifier.scopus-author-id55934387500
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isAuthorOfPublication6bbd19e6-ea9c-4502-b972-ec6997e9c481
relation.isAuthorOfPublication.latestForDiscovery6bbd19e6-ea9c-4502-b972-ec6997e9c481
relation.isProjectOfPublicationa438b9d1-8a6a-4c90-a13b-7ccf34071451
relation.isProjectOfPublication3b8a803c-37e5-4354-93f5-6410d7fb2af7
relation.isProjectOfPublication.latestForDiscoverya438b9d1-8a6a-4c90-a13b-7ccf34071451

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Poster_SPGH_PDS_IC_vFinal.pdf
Size:
633.08 KB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

DGH - Posters/abstracts em congressos internacionais