Variants in 46,XY DSD-Related Genes in Syndromic and Non-Syndromic Small for Gestational Age Children with Hypospadias

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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.authorBRAGA, B. L.
dc.contributor.authorGOMES, N. L.
dc.contributor.authorNISHI, M. Y.
dc.contributor.authorFREIRE, B. L.
dc.contributor.authorBATISTA, R. L.
dc.contributor.authorFARIA JUNIOR, J. A. D.
dc.contributor.authorFUNARI, M. F. A.
dc.contributor.authorBENEDETTI, A. F. F.
dc.contributor.authorNARCIZO, A. De Moraes
dc.contributor.authorCARDOSO, L. Cavalca
dc.contributor.authorLERARIO, A. M.
dc.contributor.authorGUERRA-JUNIOR, G.
dc.contributor.authorCOSTA, E. M. F.
dc.contributor.authorDOMENICE, S.
dc.contributor.authorJORGE, A. A. L.
dc.contributor.authorMENDONCA, B. B.
dc.date.accessioned2024-03-13T19:52:10Z
dc.date.available2024-03-13T19:52:10Z
dc.date.issued2022
dc.description.abstractHypospadias is a common congenital disorder of male genital formation. Children born small for gestational age (SGA) present a high frequency of hypospadias of undetermined etiology. No previous study investigated the molecular etiology of hypospadias in boys born SGA using massively parallel sequencing. Our objective is to report the genetic findings of a cohort of patients born SGA with medium or proximal hypospadias. We identified 46 individuals with this phenotype from a large cohort of 46,XY DSD patients, including 5 individuals with syndromic features. DNA samples from subjects were studied by either whole exome sequencing or target gene panel approach. Three of the syndromic patients have 5 main clinical features of Silver-Russell syndrome (SRS) and were first studied by MLPA. Among the syndromic patients, loss of DNA methylation at the imprinting control region H19/IGF2 was identified in 2 individuals with SRS clinical diagnosis. Two novel pathogenic variants in compound heterozygous state were identified in the CUL7 gene establishing the diagnosis of 3M syndrome in one patient, and a novel homozygous variant in TRIM37 was identified in another boy with Mulibrey nanism phenotype. Among the non-syndromic subjects, 7 rare heterozygous variants were identified in 6 DSD-related genes. However, none of the variants found can explain the phenotype by themselves. In conclusion, a genetic defect that clarifies the etiology of hypospadias was not found in most of the non-syndromic SGA children, supporting the hypothesis that multifactorial causes, new genes, and/or unidentified epigenetic defects may have an influence in this condition.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexScopus
dc.description.indexDimensions
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES
dc.identifier.citationSEXUAL DEVELOPMENT, v.16, n.1, p.27-33, 2022
dc.identifier.doi10.1159/000518091
dc.identifier.issn1661-5425
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/58604
dc.language.isoeng
dc.publisherS. KARGER AGeng
dc.relation.ispartofSexual Development
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright S. KARGER AGeng
dc.subjectAtypical genitaliaeng
dc.subjectDifferences of sex developmenteng
dc.subjectMassive parallel sequencingeng
dc.subject.otherdisorder of sex development, 46,xyeng
dc.subject.otherdna methylationeng
dc.subject.othergestational ageeng
dc.subject.otherhumanseng
dc.subject.otherhypospadiaseng
dc.subject.otherinfant, newborneng
dc.subject.otherinfant, small for gestational ageeng
dc.subject.othermaleeng
dc.subject.othertripartite motif proteinseng
dc.subject.otherubiquitin-protein ligaseseng
dc.subject.othertrim37 protein, humaneng
dc.subject.othertripartite motif proteineng
dc.subject.otherubiquitin protein ligaseeng
dc.subject.othercomplicationeng
dc.subject.otherdna methylationeng
dc.subject.othergeneticseng
dc.subject.othergestational ageeng
dc.subject.otherhumaneng
dc.subject.otherhypospadiaseng
dc.subject.othermaleeng
dc.subject.othernewborneng
dc.subject.othersmall for date infanteng
dc.titleVariants in 46,XY DSD-Related Genes in Syndromic and Non-Syndromic Small for Gestational Age Children with Hypospadiaseng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalLERARIO, A. M.:University of Michigan, Ann Arbor, MI, United States
hcfmusp.author.externalGUERRA-JUNIOR, G.:Universidade Estadual de Campinas, Campinas, Brazil
hcfmusp.citation.scopus2
hcfmusp.contributor.author-fmusphcBARBARA LEITAO BRAGA
hcfmusp.contributor.author-fmusphcNATHALIA LISBOA ROSA ALMEIDA GOMES
hcfmusp.contributor.author-fmusphcMIRIAN YUMIE NISHI
hcfmusp.contributor.author-fmusphcBRUNA LUCHEZE FREIRE
hcfmusp.contributor.author-fmusphcRAFAEL LOCH BATISTA
hcfmusp.contributor.author-fmusphcJOSE ANTONIO DINIZ FARIA JUNIOR
hcfmusp.contributor.author-fmusphcMARIANA FERREIRA DE ASSIS FUNARI
hcfmusp.contributor.author-fmusphcANNA FLAVIA FIGUEREDO BENEDETTI
hcfmusp.contributor.author-fmusphcAMANDA DE MORAES NARCIZO
hcfmusp.contributor.author-fmusphcLAIS CAVALCA CARDOSO
hcfmusp.contributor.author-fmusphcELAINE MARIA FRADE COSTA
hcfmusp.contributor.author-fmusphcSORAHIA DOMENICE
hcfmusp.contributor.author-fmusphcALEXANDER AUGUSTO DE LIMA JORGE
hcfmusp.contributor.author-fmusphcBERENICE BILHARINHO DE MENDONCA
hcfmusp.description.beginpage27
hcfmusp.description.endpage33
hcfmusp.description.issue1
hcfmusp.description.volume16
hcfmusp.origemSCOPUS
hcfmusp.origem.dimensionspub.1141009357
hcfmusp.origem.pubmed34518484
hcfmusp.origem.scopus2-s2.0-85115648206
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