Cited by 31Williams Syndrome ResearchGenomic variations and chromosomal abnormalitiesGenetics and Neurodevelopmental Disorders

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

Duba, Hans-Christoph, Doll, Andreas, Neyer, Michael, Erdel, Martin, Mann, Christian, Hammerer, Ignaz, Utermann, Gerd, Grzeschik, Karl-Heinz·2002·European Journal of Human Genetics

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.

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Crossref · 10.1038/sj.ejhg.5200812

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  1. Beuren AJ . Supravalvular aortic stenosis: a complex syndrome with and without mental retardation Birth Defects 1972 5: 45–56

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Authors
Duba, H.-C., Doll, A., Neyer, M., Erdel, M., Mann, C., Hammerer, I., Utermann, G., & Grzeschik, K.-H.
Affiliations
  • Innsbruck Medical University (AT)
  • Philipps University of Marburg (DE)
Corresponding author
Utermann, Gerd
Venue
European Journal of Human Genetics
Published
2002-06
Volume
10
Issue
6
Pages
351-361
ISSN
  • 1018-4813 (ISSN-L)
  • 1476-5438
OpenAlex
W2317609566
Cited by
31
References
39
Citations by year
2023: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2012: 2
FWCI
0.77
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Human Genetics (publishedVersion)
  • PubMed (publishedVersion)
Funders
University of Toronto
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Williams syndrome, elastin gene, chromosome 7q11.23, supravalvular aortic stenosis, haploinsufficiency, phenotypic variability, position effect, translocation breakpoints
MeSH terms
Adult, Base Sequence, Child, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 7, Cloning, Molecular, Elastin, Female, Humans, Male, Molecular Sequence Data, Pedigree, Phenotype, Translocation, Genetic, In Situ Hybridization, Fluorescence, Sequence Analysis, DNA, Williams Syndrome, Physical Chromosome Mapping

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