Abstract
The Williams-Beuren syndrome (WBS) is a complex developmental disorder with multisystemic manifestations including supravalvular aortic stenosis (SVAS), a so-called elfin face, a hoarse voice, and a specific cognitive phenotype. Most WBS patients have a >1 Mb deletion on one of their chromosomes 7 in q11 but except for elastin, whose haploinsufficiency causes the cardiovascular malformations, it is unknown which genes in the deletion area contribute to the phenotype. We have investigated a family with a cytogenetically balanced translocation t(7;16)(q11.23;q13) in which affected individuals manifested a broad spectrum of clinical phenotypes ranging from a hoarse voice as the only feature to the full WBS phenotype. Molecular cytogenetic and DNA sequence analyses of the translocation breakpoint showed that the cytogenetic rearrangement disrupts the elastin gene locus within intron 5 in the exact same manner in all translocation carriers. The recently described large inversion of the 7q11.23 region was not present in this family. Our data demonstrate that disruption of the elastin gene by a translocation breakpoint may cause classical WBS, atypical WBS, SVAS, or no recognisable phenotype, and provide a clear example for extensive phenotypic variability associated with a position effect in humans.
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Acknowledgements
We thank Drs Lucy Osborne and Steve Scherer (Department of Molecular and Medical Genetics, The University of Toronto, Ontario, Canada) for providing us with BACs CTA-208H19, RP11-815K3, CTB-139P11 and PAC R05-1186P10 for inversion screening of the WBS region. We thank Pensiri Probst, Eveline Rode and Claudia Schneider for their skilful technical assistance. This work was supported by the ‘Verein zur Förderung der Humangenetik an der Universität Innsbruck’.
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Duba, HC., Doll, A., Neyer, M. et al. The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome. Eur J Hum Genet 10, 351–361 (2002). https://doi.org/10.1038/sj.ejhg.5200812
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DOI: https://doi.org/10.1038/sj.ejhg.5200812
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