Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases

Area of Science:

• Genetics
• Molecular Cytogenetics
• Genomic Medicine

Background:

• Array Comparative Genomic Hybridization (a-CGH) is a key tool for identifying genomic imbalances.
• This study focuses on the clinical implementation of Chromosomal Microarray Analysis (CMA), a high-resolution human genome analysis technique.

Purpose of the Study:

• To evaluate the clinical utility and diagnostic yield of CMA in a large cohort of patients.
• To compare the performance of different CMA array versions (V4 and V5) in detecting genomic imbalances.

Main Methods:

• CMA was performed on 2513 postnatal samples from patients with diverse clinical phenotypes.
• Two versions of CMA arrays were used: V4 (775 samples) and V5 (1738 samples) with expanded genomic coverage.
• Results were analyzed for clinically relevant genomic imbalances, including those in patients with normal karyotypes/FISH.

Main Results:

• CMA identified clinically relevant genomic imbalances in 8.5% of patients (7.6% with V4, 8.9% with V5).
• Abnormal CMA findings were detected in 5.2% of patients with previously normal karyotypes/FISH, with V5 showing higher detection rates.
• The analysis identified 51 cryptic microdeletions and 39 microduplications associated with known genomic disorders, and copy number variations (CNVs) of uncertain significance.

Conclusions:

• CMA demonstrates significantly improved sensitivity for detecting clinically relevant genomic imbalances.
• The findings emphasize the diagnostic potential of CMA in identifying subtle genetic variations.
• Comprehensive genetic counseling is crucial for accurate clinical correlation and interpretation of CMA results.