title: 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.
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.
authors.affiliation: Institut für Medizinische Biologie und Humangenetik der Universität Innsbruck, A-6020 Innsbruck, Austria. gerd.utermann@uibk.ac.at
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Duba
authors.forename: Andreas
authors.initials: A
authors.lastname: Doll
authors.forename: Michael
authors.initials: M
authors.lastname: Neyer
authors.forename: Martin
authors.initials: M
authors.lastname: Erdel
authors.forename: Christian
authors.initials: C
authors.lastname: Mann
authors.forename: Ignaz
authors.initials: I
authors.lastname: Hammerer
authors.forename: Gerd
authors.initials: G
authors.lastname: Utermann
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Grzeschik
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D002885:Chromosomes, Human, Pair 16; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D004549:Elastin / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D020161:Physical Chromosome Mapping; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic; D018980:Williams Syndrome / Q000235:genetics*
chemical_list: D004549:Elastin