{Reference Type}: Journal Article
{Title}: A novel CHD7 variant in a chinese family with CHARGE syndrome.
{Author}: Shan Y;Yao L;Li L;Gao X;Jiang J;
{Journal}: Genes Genomics
{Volume}: 46
{Issue}: 3
{Year}: 2024 03 5
{Factor}: 2.164
{DOI}: 10.1007/s13258-023-01411-8
{Abstract}: CHARGE syndrome is a rare autosomal dominant (AD) multi-system disorder with a broad and variable clinical manifestation and occurs in approximately 1/10,000 newborns in the world. Mutations in the CHD7 gene are the genetic cause of over 90% of patients with typical CHARGE syndrome. The present study reported a novel variant in the CHD7 gene in a Chinese family with an abnormal fetus.<BR>Routine prenatal ultrasound screening showed fetal heart abnormality and left foot varus. Chromosomal microarray analysis (CMA) and fetus-parent whole-exome sequencing (trio-WES) were performed to determine the genetic cause of the fetus. The candidate variant was further verified using Sanger sequencing.<BR>CMA analysis revealed normal results. However, WES analysis identified a de novo heterozygous variant of c.2919_2922del (NM_017780.4) on exon 11 of CHD7 gene, resulting in a premature truncation of the CHD7 protein (p.Gly975*). The variant was classified as Pathogenic (PVS1 + PS2_Moderate + PM2_Supporting) based on the ACMG guidelines. Combined with the clinical phenotype of fetal heart abnormalities, it was confirmed CHARGE syndrome.<BR>We identified a novel heterozygous variant c.2919_2922del in CHD7 of a Chinese fetus with CHARGE syndrome, enriching the genotype-phenotype spectrum of CHD7. These results suggest that genetic testing could help facilitate prenatal diagnosis of CHARGE syndrome, thus promoting the appropriate genetic counseling.