Discovery of a Novel CHD7 CHARGE Syndrome Variant (c.502C>T) by Prenatal Diagnostic Analysis: A Case Report.

Objective: To analyze the clinical characteristics and genetic variations observed in fetuses with CHARGE syndrome and identify the underlying genetic causes responsible for their multisystem malformations.

Method: Amniocentesis was performed on a fetus at 21⁺⁵ weeks of gestation with multiple systemic malformations. Amniotic fluid was collected for karyotype analysis, chromosomal microarray analysis (CMA), and whole-exome sequencing (WES).

Result: The fetal karyotype and CMA results were normal; WES analysis revealed a mutation at position 61654493 on chromosome 8, specifically at the 502nd base of the gene coding sequence (c.502C>T; p.Gln168*), located in exon 2. Familial verification confirmed this as a de novo variant, as both parents exhibited wild-type alleles. In accordance with ACMG guidelines, this variant was classified as pathogenic (PVS1_VeryStrong, PS2, PS4, PM2) due to its association with multi-system abnormalities, including congenital heart defects, leading to a diagnosis of CHARGE syndrome.

Conclusions: A novel heterozygous variant in the CHD7 gene was identified, expanding the genotype-phenotype spectrum of CHD7 and providing valuable insights for genetic counseling. Mutations in the CHD7 gene may underlie multisystem malformations in fetuses. Concurrent use of CMA and WES is recommended during prenatal diagnosis to elucidate genetic causes and enhance the understanding of CHARGE syndrome.