Whole-exome sequencing in fetuses with central nervous system abnormalities

Area of Science:

• Genetics
• Prenatal Diagnosis
• Neuroscience

Background:

• Chromosomal microarray analysis (CMA) is a standard genetic test for detecting chromosomal abnormalities.
• Fetal central nervous system (CNS) abnormalities can arise from various genetic causes not always detected by CMA.

Observation:

• Whole-exome sequencing (WES) was performed on 9 fetuses with CNS abnormalities and normal CMA results.
• The study period was from 2014 to 2017.

Findings:

• Pathogenic or likely pathogenic variants were identified in 5 out of 7 cases (71%).
• Identified variants included those in TUBA1A, VRK1, ARX, and TUBB3 genes.
• A compound heterozygous state involving NPHP1 deletion was found in one family.

Implications:

• Whole-exome sequencing significantly enhances the diagnostic yield for fetal CNS abnormalities.
• WES offers a valuable tool for identifying genetic causes of structural brain malformations when CMA is negative.
• Improved genetic diagnosis can inform clinical management and genetic counseling for affected families.