Abstract
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.
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Acknowledgements
We are grateful to the patients and the parents for participation in this study. We thank Cindy Skinner, Lynn Dukes-Rimsky, Raewyn Lowe, Melissa Cook, Julianne Collins and Carlos Eduardo Frigério Domingues for providing assistance at various stages of this study. We thank Sarah H Elsea for sharing RAI1 gene primer sequences. This study was supported in part by funds from the SC Department of Disabilities and Special Needs, a fund from the Coordination for the Improvement of Higher Education Personnel (CAPES) foundation, Brazil to GHV, and a fund from the Jerome Lejeune Foundation to KW.
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Vieira, G., Rodriguez, J., Carmona-Mora, P. et al. Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith–Magenis syndrome. Eur J Hum Genet 20, 148–154 (2012). https://doi.org/10.1038/ejhg.2011.167
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DOI: https://doi.org/10.1038/ejhg.2011.167
