Abstract:

Objective To screen the elastin gene (ELN) mutations of patients with Williams syndrome (WS) or isolated supravalvular aortic stenosis (SVAS) and analyze the causes of cardiovascular variability among patients with WS and the genetic causes of the isolated SVAS. Methods Eight patients with WS and six patients with isolated SVAS were enrolled. Multiplex ligation-dependent probe amplification (MLPA) was adopted to detect the microdeletion. PCR was applied to amplify all exons of ELN gene. Direct forward and reverse sequencing was performed for all amplified fragments. The results of sequencing were compared with the sequence of elastin in GenBank by the BLAST program and possible mutations were screened. Results The microdeletion in 7q11.23 region was present in all eight patients with WS and absent in all patients with isolated SVAS and the deletion size was 1.04-1.61Mb. Among seven detected SNPs, five of them located in the intron region without involving splice-site, while another two SNPs located in exon region. The mutation c.212 C>T was detected in No. 5 exon of No.01 patient and a synonymous mutation c.1674G>A was identified in No. 25 exon of No.07 patient. Conclusion The causes of cardiovascular variability of patients with WS and the genetic causes of the isolated SVAS are complicated and need more extensive gene screening.

Key words: Williams syndrome, supravalvular aortic stenosis, elastin gene, gene mutation screening