Supravalvular aortic stenosis (SVAS) is an obstructive vascular disorder leads to congenital narrowing of large arteries. SVAS can occur sporadically or as part of Williams syndrome. Abnormalities involving the elastin gene (ELN) have been shown to cause SVAS. DNA was isolated from the peripheral blood of 22 Japanese patients who were diagnosed as having SVAS but without deletion of the (ELN) region revealed by FISH analysis. Samples were screened for mutations in all 34 exons of (ELN) using PCR-directed sequence analysis. Six truncating DNA mutations in (ELN) were found in 2 familial and 4 sporadic cases. Among them, one destroy start condon mutation (g. 2T > C), one nonsense mutation in exon 21 [g.1371C > G (p. Y457X)], three frame-shift mutations in exon 1 (g. 33delC), exon 4 (g. 183delA) and exon 9 (g.453-454insA) were identified as novel mutations. All our finding mutated genes encode the truncated proteins lacking the C-terminal conserved hydrophilic domain which is important for elastin assembly, thereby leading to the haploinsufficiency of elastin. These data indicate that nucleotide alterations of (ELN) occur in about 27.3% of SVAS patients and the mechanism by which (ELN) point mutations exert their effect is causing functional hemizygosity. Further study on remaining SVAS patients is needed for understanding of the etiology of this entity.