Clinical study of single nucleotide polymorphism-based chromosome microarray analysis in the etiological diagnosis of...

This study investigates the clinical application of single-nucleotide polymorphisms (SNP)-based chromosome microarray analysis (CMA) in the etiological diagnosis of fetal congenital heart disease (CHD). We 5,116 amniotic fluid samples collected through amniocentesis from January 2022 to December 2024 in Urumqi, Xinjiang, China. Based on fetal ultrasound findings, structural abnormalities, and specific types, CHD was categorized into four groups: isolated CHD, non-isolated CHD, non-CHD, and a normal group. The incidence of aneuploidies were highest in non-isolated CHD cases (16.91%), approximately five times higher than that in cases with isolated CHD (3.8%) (P < 0.001). The incidence of pathogenic copy number variants (CNVs) were similar across groups (2.11%-3.68%). The non-isolated CHD group demonstrated a significantly higher incidence of trisomy 21 (8.82%) and trisomy 18 (5.88%) compared to other groups (P < 0.001). Among the pathogenic CNVs, we identified five cases of deletions (22q11.2) in the isolated CHD group, eight losses (15q11.2),and 11 losses (22q11.2) in the normal group. SNP-based CMA enhances the detection of abnormal CNVs in fetuses with CHD, offering medical reference for diagnosing chromosomal etiologies and enabling precise genetic counseling. For clinical practice, SNP-based CMA should be strongly recommended for non-isolated CHD fetuses, and considered as a supplementary test for isolated CHD fetuses.