Abstract
Williams–Beuren syndrome (WBS; OMIM no. 194050) is a multisystemic neurodevelopmental disorder caused by a hemizygous deletion of 1.55 Mb on chromosome 7q11.23 spanning 28 genes. Haploinsufficiency of the ELN gene was shown to be responsible for supravalvular aortic stenosis and generalized arteriopathy, whereas LIMK1, CLIP2, GTF2IRD1 and GTF2I genes were suggested to be linked to the specific cognitive profile and craniofacial features. These insights for genotype–phenotype correlations came from the molecular and clinical analysis of patients with atypical deletions and mice models. Here we report a patient showing mild WBS physical phenotype and normal IQ, who carries a shorter 1 Mb atypical deletion. This rearrangement does not include the GTF2IRD1 and GTF2I genes and only partially the BAZ1B gene. Our results are consistent with the hypothesis that hemizygosity of the GTF2IRD1 and GTF2I genes might be involved in the facial dysmorphisms and in the specific motor and cognitive deficits observed in WBS patients.
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Acknowledgements
We are grateful to the family who participated in the study. This work was supported by grants from the Jérôme Lejeune Foundation, the Telethon Action Suisse Foundation, the Novartis Foundation, the Swiss National Science Foundation and the European commission (anEUploidy grant 037627) to AR, by grants from the Italian Ministry of Health (Ricerca Corrente 2007–09), the Fondazione Banca del Monte di Foggia ‘Domenico Siniscalco Ceci’, the Italian Telethon Foundation (Grant N. GGP06122), the Jérôme Lejeune Foundation and Italian Foreign Office to GM, Compagnia di San Paolo and Fondazione CRT, Torino to GBF.
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Ferrero, G., Howald, C., Micale, L. et al. An atypical 7q11.23 deletion in a normal IQ Williams–Beuren syndrome patient. Eur J Hum Genet 18, 33–38 (2010). https://doi.org/10.1038/ejhg.2009.108
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DOI: https://doi.org/10.1038/ejhg.2009.108
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