Dr. Stuart Shapira from the Baylor College of Medicine requests two years of support to lay the groundwork to examine the genotypic basis for a number of abnormalities associated with terminal or interstitial deletions involving the tip of the short arm of chromosome 1, 1p36. Children who are hemizygous for 1p36 deletion exhibit a spectrum of phenotypes, the most common being mental retardation, hypotonia, and developmental delay. There is evidence that the deletions are heterogeneous and this fact, coupled with the heterogeneity of phenotypic manifestations, suggests that haploinsufficiency or the uncovering of recessive mutations might be responsible for the phenotypes. There is also evidence that this is a contiguous gene syndrome. Dr. Shapira and his colleagues identified six patients during a single year. Based on the number of newborns examined, Dr. Shapira feels that the incidence of this disorder might be 1/10,000--much higher than previously thought. Since children with these deletions do have variable phenotypes, it is important for the patients to be examined by a single clinical team to make sure the assessment criteria are uniform. Such clinical examination is the first aim of the proposal. In the remaining part of the study, the investigator proposes to identify and map the critical regions of several features of the 1p36 deletion syndrome.
| Heilstedt, H A; Burgess, D L; Anderson, A E et al. (2001) Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome. Epilepsia 42:1103-11 |
| Heilstedt, H A; Shapira, S K; Gregg, A R et al. (1999) Molecular and clinical characterization of a patient with duplication of 1p36.3 and metopic synostosis. Clin Genet 56:123-8 |
| Wu, Y Q; Heilstedt, H A; Bedell, J A et al. (1999) Molecular refinement of the 1p36 deletion syndrome reveals size diversity and a preponderance of maternally derived deletions. Hum Mol Genet 8:313-21 |
