Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome

Abstract

Williams syndrome (WS) is a developmental disorder affecting connective tissue and the central nervous system. A common feature of WS, supravalvular aortic stenosis, is also a distinct autosomal dominant disorder caused by mutations in the elastin gene. In this study, we identified hemizygosity at the elastin locus using genetic analyses in four familial and five sporadic cases of WS. Fluorescent in situ hybridization and quantitative Southern analyses confirmed these findings, demonstrating inherited and de novo deletions of the elastin gene. These data indicate that deletions involving one elastin allele cause WS and implicate elastin hemizygosity in the pathogenesis of the disease.

The subcellular localization of the ChoRE-binding protein, encoded by the Williams–Beuren syndrome critical region gene 14, is regulated by 14-3-3

“…It is thus a challenge to determine which of the WBS hemizygote genes causes the various phenotypes of the syndrome (18,19,34,35). ELN haploinsufficiency has been linked to supravalvular aortic and other stenoses (21,36,37), whereas a mouse model suggests that CYLN2 hemizygosity might contribute to the WBS cognitive profile (38). Furthermore, the study of WBS patients with atypical deletion suggests that GTF2IRD1, GTF2I and CYLN2 genes might contribute to the visual spatial processing deficits harbored by WBS patients (39,40).…”

Using developmental trajectories to examine verbal and visuospatial short-term memory development in children and adolescents with Williams and Down syndromes

“…This normally includes the elastin gene (e.g. Ewart et al, 1993;Lowery et al, 1995). Physically, WS is primarily characterised by distinct facial dysmorphia, and other musculoskeletal, cardiovascular, and renal abnormalities (e.g.…”

Zebrafish gene knockdowns imply roles for human YWHAG in infantile spasms and cardiomegaly

“…ncbi.nlm.nih.gov/Omim/) caused by hemizygosity of chromosome 7q11.23 (Ewart et al, 1993). WBS patients show mental retardation with a specific cognitive-behavioral profile, supravalvular aortic stenosis, infantile hypercalcemia, a hoarse voice, and distinctive dysmorphic features including an elfin-like face and edematous eyes.…”

“…WBS patients show mental retardation with a specific cognitive-behavioral profile, supravalvular aortic stenosis, infantile hypercalcemia, a hoarse voice, and distinctive dysmorphic features including an elfin-like face and edematous eyes. The prevalence of WBS in the population is approximately one in 7,500-20,000 (Ewart et al, 1993;Stromme et al, 2002;Wu et al, 1998). Almost all deletions of 7q11.23 in patients with WBS have arisen by de novo mechanisms.…”