Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis

Area of Science:

• Medical Genetics
• Genomics
• Neonatal Medicine

Background:

• Birth defects affect a significant number of neonates, often stemming from underlying genomic imbalances.
• Accurate diagnosis is crucial for effective management and genetic counseling.

Purpose of the Study:

• To determine the frequency of genomic imbalances in neonates with birth defects using chromosomal microarray analysis (CMA).
• To evaluate the diagnostic yield of CMA compared to traditional karyotyping.

Main Methods:

• Targeted array-based comparative genomic hybridization (chromosomal microarray analysis) was performed on 638 neonates with birth defects.
• Three versions of CMA (V5, V6, V6 Oligo) with increasing genomic coverage were utilized.
• The study focused on interrogating over 150 disease loci, with enhanced focus on rearrangement-prone regions.

Main Results:

• Chromosomal microarray analysis detected clinically significant genomic abnormalities in 17.1% of neonates.
• Detection rates varied by CMA version (13.7% to 19.9%) and clinical indication, with rates up to 66.7% for specific indications.
• The analysis identified chromosomal aneuploidies (2.5%), segmental aneusomies (12.7%), and chromosomal mosaicism (1.9%).

Conclusions:

• Chromosomal microarray analysis is a powerful clinical tool for precise and rapid identification of genomic imbalances causing birth defects.
• CMA detects a higher number of clinically relevant genomic abnormalities than conventional cytogenetic methods.
• This enables timely molecular diagnoses, informed clinical decision-making, and accurate recurrence risk assessment.