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Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies

2018-05-10Journal article Open access
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dc.contributor.authorJorge, P.
dc.contributor.authorGarcia, E.
dc.contributor.authorGonçalves, A.
dc.contributor.authorMarques, I.
dc.contributor.authorMaia, N.
dc.contributor.authorRodrigues, B.
dc.contributor.authorSantos, H.
dc.contributor.authorFonseca, J.
dc.contributor.authorSoares, G.
dc.contributor.authorCorreia, C.
dc.contributor.authorReis-Lima, M.
dc.contributor.authorCirigliano, V.
dc.contributor.authorSantos, R.
dc.date.accessioned2019-07-18T09:52:20Z
dc.date.available2019-07-18T09:52:20Z
dc.date.issued2018-05-10
dc.description.abstractBACKGROUND: We describe a female infant with Fragile-X syndrome, with a fully expanded FMR1 allele and preferential inactivation of the homologous X-chromosome carrying a de novo deletion. This unusual and rare case demonstrates the importance of a detailed genomic approach, the absence of which could be misguiding, and calls for reflection on the current clinical and diagnostic workup for developmental disabilities. CASE PRESENTATION: We present a female infant, referred for genetic testing due to psychomotor developmental delay without specific dysmorphic features or relevant family history. FMR1 mutation screening revealed a methylated full mutation and a normal but inactive FMR1 allele, which led to further investigation. Complete skewing of X-chromosome inactivation towards the paternally-inherited normal-sized FMR1 allele was found. No pathogenic variants were identified in the XIST promoter. Microarray analysis revealed a 439 kb deletion at Xq28, in a region known to be associated with extreme skewing of X-chromosome inactivation. CONCLUSIONS: Overall results enable us to conclude that the developmental delay is the cumulative result of a methylated FMR1 full mutation on the active X-chromosome and the inactivation of the other homologue carrying the de novo 439 kb deletion. Our findings should be taken into consideration in future guidelines for the diagnostic workup on the diagnosis of intellectual disabilities, particularly in female infant cases.pt_PT
dc.description.sponsorshipDr. Paula Jorge received a research grant “Bolsa de Investigação DEFI 2015”, CHP, E.P.E.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBMC Med Genet. 2018 May 10;19(1):74pt_PT
dc.identifier.doi10.1186/s12881-018-0589-6pt_PT
dc.identifier.issn1471-2350
dc.identifier.urihttp://hdl.handle.net/10400.16/2273
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relation.publisherversionhttps://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-018-0589-6pt_PT
dc.subjectDevelopmental disabilities in femalespt_PT
dc.subjectFMR1 methylated full mutationpt_PT
dc.subjectFragile-X syndromept_PT
dc.subjectSkewing of X-chromosome inactivationpt_PT
dc.subjectXq28 deletionpt_PT
dc.titleClassical fragile-X phenotype in a female infant disclosed by comprehensive genomic studiespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F00215%2F2013/PT
oaire.citation.conferencePlaceEnglandpt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage74pt_PT
oaire.citation.titleBMC Medical Geneticspt_PT
oaire.citation.volume19pt_PT
oaire.fundingStream5876
person.familyNameJorge
person.familyNameMaia
person.givenNamePaula
person.givenNameNuno
person.identifier.ciencia-idFD15-9412-CF3F
person.identifier.ciencia-id4816-1492-FEB1
person.identifier.orcid0000-0002-6507-222X
person.identifier.orcid0000-0003-3274-2474
person.identifier.scopus-author-id7005566496
person.identifier.scopus-author-id57193114189
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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