Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith-Magenis syndrome
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2012-02-01
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Smith-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.
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17p11.2, arrayCGH, deletion, mutation, RAI1, Smith-Magenis syndrome, G protein coupled receptor, retinoic acid induced 1, unclassified drug, adolescent, adult, cellular distribution, child, chromosome 17p, clinical article, clinical feature, comparative genomic hybridization, female, fluorescence in situ hybridization, gene deletion, gene mutation, genetic screening, human, male, molecular weight, phenotype, polymerase chain reaction, priority journal, school child, Smith Magenis syndrome, transcription initiation, Adolescent, Adult, Amino Acid Sequence, Base Sequence, Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 17, DNA Copy Number Variations, Facies, Female, Genetic Association Studies, Genotype, Humans, Male, Mutation, Phenotype, Sequence Deletion, Smith-Magenis Syndrome, Transcription Factors, Young Adult
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European Journal of Human Genetics, v. 20, n. 2, p. 148-154, 2012.