Supravalvular Aortic Stenosis Caused by a Familial Chromosome 7 Inversion Disrupting the < b > < i > ELN < /i > < /b > Gene Uncovered by Whole-Genome Sequencing

We report herein the case of a 4-year-old boy presenting with clinically isolated supravalvular aortic stenosis (SVAS). No chromosomal imbalance was detected by array CGH. The karyotype showed a balanced paracentric chromosome 7 inversion. Breakpoint characterization using paired-end whole-genome sequencing (WGS) revealed anELNgene disruption in intron 1, accounting for the phenotype. Family study showed that the inversion was inherited, with incomplete penetrance. To our knowledge, this is the first case of a disruption of theELN gene characterized by WGS. It contributes to refine the genotype-phenotype correlation inELN disruption. Although this disruption is a rare etiology of SVAS, it cannot be detected by the diagnostic tests usually performed, such as array CGH or sequencing methods (Sanger, panel, or exome sequencing). With the future perspective of WGS as a diagnostic tool, it will be important to include a structural variation analysis in order to detect balanced rearrangements and gene disruption.Mol Syndromol
Source: Molecular Syndromology - Category: Molecular Biology Source Type: research