ABSTRACT
Fluorescence in situ hybridisation (FISH) and conventional chromosome analysis were performed on a series of 52 patients with classical Williams-Beuren syndrome (WBS), suspected WBS, or supravalvular aortic stenosis (SVAS). In the classical WBS group, 22/23 (96%) had a submicroscopic deletion of the elastin locus on chromosome 7, but the remaining patient had a unique interstitial deletion of chromosome 11 (del(11)(q13.5q14.2)). In the suspected WBS group 2/22 (9%) patients had elastin deletions but a third patient had a complex karyotype including a ring chromosome 22 with a deletion of the long arm (r(22)(p11-->q13)). In the SVAS group, 1/7 (14%) had an elastin gene deletion, despite having normal development and minimal signs of WBS. Overall, some patients with submicroscopic elastin deletions have fewer features of Williams-Beuren syndrome than those with other cytogenetic abnormalities. These results, therefore, emphasise the importance of a combined conventional and molecular cytogenetic approach to diagnosis and suggest that the degree to which submicroscopic deletions of chromosome 7 extend beyond the elastin locus may explain some of the phenotypic variability found in Williams-Beuren syndrome.
Subject(s)
Chromosome Deletion , Genetic Variation , Williams Syndrome/genetics , Child , Child, Preschool , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 22/genetics , Chromosomes, Human, Pair 7/genetics , Elastin/genetics , Female , Gene Deletion , Genotype , Humans , In Situ Hybridization, Fluorescence , Infant , Male , Phenotype , Pulmonary Valve Stenosis , Ring Chromosomes , Williams Syndrome/diagnosisABSTRACT
Bovine intestinal mucosal alkaline phosphatase is inactivated by the chelating agent EGTA. Several concentrations of the enzyme were incubated with EGTA and a range of concentrations of the substrate p-nitrophenyl phosphate to determine the substrate concentration as a function of time. As predicted by a recently developed theory [Duggleby (1986) J. Theor. Biol. 123, 67-80], catalysis ceases before all substrate is exhausted. An analysis of these final substrate concentrations according to the theory revealed that, whereas the free enzyme is unstable, the effect of EGTA is counteracted when either the substrate or product (phosphate) is bound. Comparison of the results with those obtained by direct stability measurements and steady-state kinetic experiments gave a qualitatively and quantitatively consistent body of evidence in support of this interpretation.
