Pathogenic recurrent copy number variants in 7,078 pregnancies via chromosomal microarray analysis

Area of Science:

• Prenatal Genetics
• Medical Diagnostics
• Human Genetics

Background:

• Copy Number Variations (CNVs) are a significant cause of genetic disorders.
• Recurrent CNVs, often arising from segmental duplications, are implicated in various congenital anomalies.
• Understanding the incidence and spectrum of pathogenic recurrent CNVs in prenatal diagnostics is crucial.

Purpose of the Study:

• To determine the frequency of pathogenic recurrent CNVs across different fetal referral indications.
• To correlate specific CNVs with their observed intrauterine phenotypic features.
• To compare prenatal CNV profiles with known postnatal findings.

Main Methods:

• Chromosome microarray analysis (CMA) was performed on 7,078 amniotic fluid samples.
• Samples with pathogenic recurrent CNVs were further analyzed.
• Statistical analysis was used to compare incidence rates across maternal age groups.

Main Results:

• The highest incidence of pathogenic recurrent CNVs was 2.25% in the fetal ultrasound anomalies (FUA) group.
• Advanced maternal age (≥35 years) showed a lower incidence of pathogenic recurrent CNVs compared to younger mothers (p<0.05).
• Common CNVs identified included 22q11.2 (microdeletion/duplication), 1q21.1 (microdeletion/duplication), and 16p13.11 (microdeletion/duplication).

Conclusions:

• Pathogenic recurrent CNVs are more frequently detected in fetuses with fetal ultrasound anomalies.
• Pregnant women of advanced maternal age exhibit a reduced incidence of pathogenic recurrent CNVs.
• The spectrum of pathogenic recurrent CNVs differs between prenatal and postnatal diagnoses, notably for 22q11.2, 1q21.1, 15q13.3, and 15q11.2 regions.