Diagnostic utility of array-based comparative genomic hybridization in a clinical setting

Area of Science:

• Genetics
• Molecular Biology
• Clinical Cytogenetics

Background:

• Array-based comparative genomic hybridization (aCGH) is a technique for detecting genomic imbalances.
• Targeted aCGH platforms analyze specific, clinically relevant genomic loci.
• Clinical utility of targeted aCGH for cytogenetic diagnosis requires evaluation.

Purpose of the Study:

• To assess the utility of a targeted aCGH platform in a clinical setting.
• To evaluate the diagnostic yield of targeted aCGH in patients with suspected chromosomal abnormalities.

Main Methods:

• Retrospective review of 373 patients with normal chromosomal analysis tested with targeted aCGH.
• Analysis of medical records from Children's Hospital Boston (November 2004 - October 2005).
• Correlation of aCGH results with clinical presentation (e.g., developmental delay, dysmorphism).

Main Results:

• Abnormal aCGH results were found in 9.7% of patients (36/373).
• Potentially pathogenetic genomic imbalances identified in 5.4% (20/373) of patients.
• Higher detection rates of pathogenetic imbalances observed in patients with developmental delay, facial dysmorphism, or multiple congenital anomalies.

Conclusions:

• Targeted array-based comparative genomic hybridization is a clinically useful test for evaluating patients with suspected chromosomal disorders.
• Targeted aCGH serves as an effective adjunct to chromosomal analysis, particularly when a definitive genetic diagnosis is not achieved.
• The test demonstrates utility in identifying submicroscopic genomic imbalances contributing to various clinical phenotypes.