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.
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.
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.
方法:常规产前超声筛查显示胎儿心脏异常和左足内翻。进行染色体微阵列分析(CMA)和胎儿-亲本全外显子组测序(trio-WES)以确定胎儿的遗传原因。使用Sanger测序进一步验证候选变体。
结果:CMA分析显示结果正常。然而,WES分析确定了CHD7基因外显子11上c.2919_2922del(NM_017780.4)的从头杂合变体,导致CHD7蛋白的过早截短(p。Gly975*)。基于ACMG指南,该变体被分类为致病性(PVS1+PS2_中度+PM2_支持)。结合胎儿心脏异常的临床表型,它被证实为CHARGE综合征。
结论:我们在CHARGE综合征的中国胎儿CHD7中发现了一种新的杂合变体c.2919_2922del,丰富CHD7的基因型-表型谱。这些结果表明,基因检测可以帮助促进CHARGE综合征的产前诊断,从而促进适当的遗传咨询。