Williams Beuren syndrome (WBS, OMIM#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, while LIMK1, CYLN2 and GTF2IRD1 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. We report the detailed clinical and cognitive examinations together with cytogenetics (FISH) and molecular (QPCR) analysis of a WBS patient showing mild WBS physical phenotype and normal IQ. He carries a shorter 1 Mb atypical deletion, which does not include the GTF2IRD1 and GTF2I genes and only partially the BAZ1B gene. Our results are consistent with the previous 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.
An atypical 7q11.23 deletion in a normal IQ Williams-Beurensyndrome patient
BIAMINO, ELISA;FORZANO, Serena;CIRILLO, Margherita;FERRERO, Giovanni Battista;
2009-01-01
Abstract
Williams Beuren syndrome (WBS, OMIM#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, while LIMK1, CYLN2 and GTF2IRD1 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. We report the detailed clinical and cognitive examinations together with cytogenetics (FISH) and molecular (QPCR) analysis of a WBS patient showing mild WBS physical phenotype and normal IQ. He carries a shorter 1 Mb atypical deletion, which does not include the GTF2IRD1 and GTF2I genes and only partially the BAZ1B gene. Our results are consistent with the previous 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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