Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith–Magenis syndrome
| Autor: | Barbara R. DuPont, Lei Cao, Bruno F. Gamba, Daniel R. Carvalho, Suely Rodrigues dos Santos, Katherina Walz, Andréa de Rezende Duarte, Paulina Carmona-Mora, D. H. Souza, Anand K. Srivastava, Jayson Rodriguez, Danilo Moretti-Ferreira, Gustavo Henrique Apolinário Vieira |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Nonsynonymous substitution Adolescent DNA Copy Number Variations Genotype Retinoic acid induced 1 Mutant Gene mutation Biology Bioinformatics medicine.disease_cause Article Young Adult Genetics medicine Humans Amino Acid Sequence Child Genetic Association Studies Genetics (clinical) Sequence Deletion Mutation Base Sequence medicine.diagnostic_test Facies Smith–Magenis syndrome medicine.disease Phenotype Child Preschool Speech delay Trans-Activators Female Chromosome Deletion Smith-Magenis Syndrome medicine.symptom Chromosomes Human Pair 17 Transcription Factors Fluorescence in situ hybridization |
| Zdroj: | European Journal of Human Genetics. 20:148-154 |
| ISSN: | 1476-5438 1018-4813 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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