Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith-Magenis syndrome

Vieira, Gustavo H.Rodriguez, Jayson D.Carmona-Mora, PaulinaCao, LeiGamba, Bruno F.Carvalho, Daniel R.Duarte, Andréa de RezendeSantos, Suely R.Souza, Deise H. deDupont, Barbara R.Walz, KatherinaMoretti-Ferreira, DaniloSrivastava, Anand K.2014-05-272014-05-272012-02-01European Journal of Human Genetics, v. 20, n. 2, p. 148-154, 2012.1018-48131476-5438http://hdl.handle.net/11449/73177Smith-Magenis syndrome (SMS) is a complex disorder whose clinical features include mild to severe intellectual disability with speech delay, growth failure, brachycephaly, flat midface, short broad hands, and behavioral problems. SMS is typically caused by a large deletion on 17p11.2 that encompasses multiple genes including the retinoic acid induced 1, RAI1, gene or a mutation in the RAI1 gene. Here we have evaluated 30 patients with suspected SMS and identified SMS-associated classical 17p11.2 deletions in six patients, an atypical deletion of ∼139 kb that partially deletes the RAI1 gene in one patient, and RAI1 gene nonsynonymous alterations of unknown significance in two unrelated patients. The RAI1 mutant proteins showed no significant alterations in molecular weight, subcellular localization and transcriptional activity. Clinical features of patients with or without 17p11.2 deletions and mutations involving the RAI1 gene were compared to identify phenotypes that may be useful in diagnosing patients with SMS. © 2012 Macmillan Publishers Limited All rights reserved.148-154eng17p11.2arrayCGHdeletionmutationRAI1Smith-Magenis syndromeG protein coupled receptorretinoic acid induced 1unclassified drugadolescentadultcellular distributionchildchromosome 17pclinical articleclinical featurecomparative genomic hybridizationfemalefluorescence in situ hybridizationgene deletiongene mutationgenetic screeninghumanmalemolecular weightphenotypepolymerase chain reactionpriority journalschool childSmith Magenis syndrometranscription initiationAdolescentAdultAmino Acid SequenceBase SequenceChildChild, PreschoolChromosome DeletionChromosomes, Human, Pair 17DNA Copy Number VariationsFaciesFemaleGenetic Association StudiesGenotypeHumansMaleMutationPhenotypeSequence DeletionSmith-Magenis SyndromeTranscription FactorsYoung AdultDetection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith-Magenis syndromeArtigo10.1038/ejhg.2011.167Acesso restrito2-s2.0-848558173780000-0002-9256-7623