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Phenotype and genotype in 101 males with X-linked creatine transporter deficiency

2013-07Journal article Restricted access
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dc.contributor.authorvan de Kamp, J.M.
dc.contributor.authorBetsalel, O.T.
dc.contributor.authorMercimek-Mahmutoglu, S.
dc.contributor.authorAbulhoul, L.
dc.contributor.authorGrünewald, S.
dc.contributor.authorAnselm, I.
dc.contributor.authorAzzouz, H.
dc.contributor.authorBratkovic, D.
dc.contributor.authorde Brouwer, A.
dc.contributor.authorHamel, B.
dc.contributor.authorKleefstra, T.
dc.contributor.authorYntema, H.
dc.contributor.authorCampistol, J.
dc.contributor.authorVilaseca, M.A.
dc.contributor.authorCheillan, D.
dc.contributor.authorD'Hooghe, M.
dc.contributor.authorDiogo, L.
dc.contributor.authorGarcia, P.
dc.contributor.authorValongo, C.
dc.contributor.authorFonseca, M.
dc.contributor.authorFrints, S.
dc.contributor.authorWilcken, B.
dc.contributor.authorvon der Haar, S.
dc.contributor.authorMeijers-Heijboer, H.E.
dc.contributor.authorHofstede, F.
dc.contributor.authorJohnson, D.
dc.contributor.authorKant, S.G.
dc.contributor.authorLion-Francois, L.
dc.contributor.authorPitelet, G.
dc.contributor.authorLongo, N.
dc.contributor.authorMaat-Kievit, J.A.
dc.contributor.authorMonteiro, J.P.
dc.contributor.authorMunnich, A.
dc.contributor.authorMuntau, A.C.
dc.contributor.authorNassogne, M.C.
dc.contributor.authorOsaka, H.
dc.contributor.authorOunap, K.
dc.contributor.authorPinard, J.M.
dc.contributor.authorQuijano-Roy, S.
dc.contributor.authorPoggenburg, I.
dc.contributor.authorPoplawski, N.
dc.contributor.authorAbdul-Rahman, O.
dc.contributor.authorRibes, A.
dc.contributor.authorArias, A.
dc.contributor.authorYaplito-Lee, J.
dc.contributor.authorSchulze, A.
dc.contributor.authorSchwartz, C.E.
dc.contributor.authorSchwenger, S.
dc.contributor.authorSoares, G.
dc.contributor.authorSznajer, Y.
dc.contributor.authorValayannopoulos, V.
dc.contributor.authorVan Esch, H.
dc.contributor.authorWaltz, S.
dc.contributor.authorWamelink, M.M.
dc.contributor.authorPouwels, P.J.
dc.contributor.authorErrami, A.
dc.contributor.authorvan der Knaap, M.S.
dc.contributor.authorJakobs, C.
dc.contributor.authorMancini, G.M.
dc.contributor.authorSalomons, G.S.
dc.date.accessioned2014-04-03T17:13:50Z
dc.date.available2014-04-03T17:13:50Z
dc.date.issued2013-07
dc.description.abstractBACKGROUND: Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, genotype and phenotype--genotype correlation has been lacking. METHODS: We performed a retrospective study of clinical, biochemical and molecular genetic data of 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic mutation in the creatine transporter gene (SLC6A8). RESULTS AND CONCLUSIONS: Most patients developed moderate to severe intellectual disability; mild intellectual disability was rare in adult patients. Speech language development was especially delayed but almost a third of the patients were able to speak in sentences. Besides behavioural problems and seizures, mild to moderate motor dysfunction, including extrapyramidal movement abnormalities, and gastrointestinal problems were frequent clinical features. Urinary creatine to creatinine ratio proved to be a reliable screening method besides MR spectroscopy, molecular genetic testing and creatine uptake studies, allowing definition of diagnostic guidelines. A third of patients had a de novo mutation in the SLC6A8 gene. Mothers with an affected son with a de novo mutation should be counselled about a recurrence risk in further pregnancies due to the possibility of low level somatic or germline mosaicism. Missense mutations with residual activity might be associated with a milder phenotype and large deletions extending beyond the 3' end of the SLC6A8 gene with a more severe phenotype. Evaluation of the biochemical phenotype revealed unexpected high creatine levels in cerebrospinal fluid suggesting that the brain is able to synthesise creatine and that the cerebral creatine deficiency is caused by a defect in the reuptake of creatine within the neuronespor
dc.identifier.citationJ Med Genet. 2013 Jul;50(7):463-72. doi: 10.1136/jmedgenet-2013-101658. Epub 2013 May 3por
dc.identifier.issn0022-2593
dc.identifier.otherdoi: 10.1136/jmedgenet-2013-101658
dc.identifier.urihttp://hdl.handle.net/10400.18/2230
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherBMJ Publishing Grouppor
dc.relation.publisherversionhttp://jmg.bmj.com/content/50/7/463.abstractpor
dc.subjectDoenças Genéticaspor
dc.subjectTransportador da Creatinapor
dc.subjectDiagnosispor
dc.subjectIntellectual Disabilitypor
dc.subjectPrognosispor
dc.subjectSLC6A8por
dc.subjectGenetic Counsellingpor
dc.titlePhenotype and genotype in 101 males with X-linked creatine transporter deficiencypor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage472por
oaire.citation.startPage463por
oaire.citation.titleJournal of Medical Geneticspor
oaire.citation.volume50(7)por
rcaap.rightsembargoedAccesspor
rcaap.typearticlepor

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