Congenital heart disease: Molecular diagnostics of supravalvular aortic stenosis.

Supravalvular aortic stenosis (SVAS) is a congenital heart disease that can occur as an isolated autosomal-dominant condition or as part of the developmental disorder Williams-Beuren syndrome (WBS) and is caused by heterozygous genetic lesions involving the elastin (ELN) gene locus on chromosome 7ql 1.23. SVAS is one of many phenotypic features associated with the contiguous gene microdeletion disorder, WBS, and is caused by deletion of the ELN locus on one chromosome 7 homolog. Point mutations, chromosomal deletions, and translocation involving ELN have also been described in individuals with nonsyndromic SVAS. In addition, ELN is involved in the connective tissue disorder, autosomal-dominant cutis laxa, and has been implicated as a susceptibility gene for hypertension and intracranial aneurysms. The molecular analysis of ELN defects is, therefore, an area of significant interest. Genetic screening can be achieved using a variety of techniques to detect both mutations and gross chromosome rearrangements involving the ELN locus, providing the ability to screen families and individuals with SVAS and associated elastinopathies.

[1]  D. Young,et al.  FAMILIAL SUPRAVALVULAR AORTIC STENOSIS. , 1964, American journal of diseases of children.

[2]  Colleen A. Morris,et al.  The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis , 1993, Cell.

[3]  J. Attwood,et al.  Description of a dinucleotide repeat polymorphism in the human elastin gene and its use to confirm assignment of the gene to chromosome 7 , 1993, Annals of human genetics.

[4]  S. Puig,et al.  A novel elastin gene mutation resulting in an autosomal dominant form of cutis laxa. , 2004, Archives of dermatology.

[5]  K. Takakura,et al.  Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11. , 2001, American journal of human genetics.

[6]  S. Thibodeau,et al.  Supravalvular aortic stenosis: a splice site mutation within the elastin gene results in reduced expression of two aberrantly spliced transcripts , 1999, Human Genetics.

[7]  K. Csiszȧr,et al.  A tetranucleotide repeat polymorphism within the human elastin gene (ELNi1) , 1997, Clinical genetics.

[8]  B. Emanuel,et al.  From microscopes to microarrays: dissecting recurrent chromosomal rearrangements , 2007, Nature Reviews Genetics.

[9]  J. B. Lowe,et al.  Supravalvular Aortic Stenosis , 1961, Circulation.

[10]  A. Munnich,et al.  Isolated supravalvular aortic stenosis: functional haploinsufficiency of the elastin gene as a result of nonsense-mediated decay , 2000, Human Genetics.

[11]  B J Bassam,et al.  Fast and sensitive silver staining of DNA in polyacrylamide gels. , 1991, Analytical biochemistry.

[12]  W. Reardon,et al.  Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis. , 1997, Human molecular genetics.

[13]  D. Chitayat,et al.  Connection between elastin haploinsufficiency and increased cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome. , 2002, American journal of human genetics.

[14]  C. Cytrynbaum,et al.  Elastin: mutational spectrum in supravalvular aortic stenosis , 2000, European Journal of Human Genetics.

[15]  C. Morris,et al.  Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis. , 1997, Human molecular genetics.

[16]  J. Belmont,et al.  Supravalvular aortic stenosis: genetic and molecular dissection of a complex mutation in the elastin gene , 2001, Human Genetics.

[17]  M. Tassabehji,et al.  An elastin gene mutation producing abnormal tropoelastin and abnormal elastic fibres in a patient with autosomal dominant cutis laxa. , 1998, Human molecular genetics.

[18]  C A Morris,et al.  Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene. , 1994, The Journal of clinical investigation.

[19]  J M Davidson,et al.  Cutis Laxa Arising from Frameshift Mutations in Exon 30 of the Elastin Gene (ELN)* , 1999, The Journal of Biological Chemistry.

[20]  S. Thibodeau,et al.  A 30 kb deletion within the elastin gene results in familial supravalvular aortic stenosis. , 1995, Human molecular genetics.

[21]  A. Karmiloff-Smith,et al.  Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes. , 1999, American journal of human genetics.

[22]  E. Kawashima,et al.  Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[23]  U. Kucich,et al.  Structure of the elastin gene and alternative splicing of elastin mRNA: implications for human disease. , 1989, American journal of medical genetics.