The genotype-phenotype correlation studies have demonstrated that WS is a contiguous gene syndrome. Deletion of different genes account for different aspects of the phenotype. Elastin hemizygosity has been proved to cause the cardiovascular disease. There is strong evidence that LIMK1 is important in visuospatial constructive cognition and that hemizygous CTF2I deletion negatively affects IQ in Williams syndrome.
Future studies should examine the role of other genes in the Williams syndrome region. Some do not contribute to the phenotype because for some gene pairs one working copy is sufficient for a normal phenotype. Hemizygosity of other deleted genes may contribute to anxiety and ADHD, which are common behavioral traits in the Williams syndrome population. Continued technological advances will refine the methods for determining deletion breakpoints, and study of additional rare families with unusual deletions in the Williams syndrome region will contribute to our knowledge of genotype-phenotype correlations in this region.
Preparation of this manuscript was supported by grant #NS35102 from the National Institute of Neurological Disorders and Stroke. The research is made possible by the generous participation of families with genetic conditions, and by the collaboration of Carolyn Mervis, Holly Hobart, Ron Gregg, and Mark Keating.
Bayes, M., Magano, L. F., Rivera, N., Flores, R., & Perez-Jurado, L. A. (2003). Mutational mechanisms of Williams-Beuren syndrome deletions. American journal of Human Genetics, 73, 131–151.
Bellugi, U., Marks, S., Bihrle, A., & Sabo, H. (1988). Dissociation between language and cognitive functions in Williams syndrome. In D. Bishop & K. Mogford (Eds.), Language development in exceptional circumstances (pp. 177–189). London: Churchill Livingstone.
Beuren, A. J. (1972). Supravalvular aortic stenosis: A complex syndrome with and without mental retardation. Birth Defects Original Article Series, 8(5), 45–56.
Botta, A., Novelli, G., Mari, A., Novelli, A., Sabini, M., Korenberg, J., Osborne, L. R., Digilio, M. C, Giannotti, A., & Dallapiccola, B. (1999). Detection of an atypical 7qll.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes. Journal of Medical Genetics, 36, 478–480.
Conway, E. E., Noonan, J., Marion, R. W., & Steeg, C. N. (1990). Myocardial infarction leading to sudden death in the Williams syndrome: Report of three cases. Journal of Pediatrics, 117, 593–595.
Curran, M. E., Atkinson, D. L., Ewart, A. K., Morris, C. A., Leppert, M. F., & Keating, M. T. (1993). The elastin gene is disrupted by a translocation associated with supravalvar aortic stenosis. Cell, 73, 159–168.