Abstract:
:Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Li DY,Toland AE,Boak BB,Atkinson DL,Ensing GJ,Morris CA,Keating MTdoi
10.1093/hmg/6.7.1021subject
Has Abstractpub_date
1997-07-01 00:00:00pages
1021-8issue
7eissn
0964-6906issn
1460-2083pii
dda145journal_volume
6pub_type
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