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.
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People with atypical deletions and varying degrees of craniofacial abnormalities implicate both proximal and distal ends of the deletion, suggesting that more than one gene is responsible.
“People with atypical deletions, and varying degrees of craniofacial abnormalities, implicate both proximal and distal ends of the deletion, suggesting that more than one gene is responsible [36-41].”
From A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development (2008) · cites this paper as [37]
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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
- Licence
- www.springer.com/tdm (tdm)
- 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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