0845 A new and accurate genetic test for unbalanced genomic defects

Array comparative genomic hybridization, also known as chromosomal microarray analysis (CMA) is a technique enabling high-resolution, genome-wide screening of segmental genomic copy number variations. Most of the published work over the past couple of years has emanated from the Genetics Department at Baylor University in Houston, Texas. CMA detects aneuploidies, well-characterized microdeletion/ microduplication syndromes and subtelomeric or other unbalanced chromosomal rearrangements i.e. this technology is not able to identify balanced chromosomal imbalances such as translocations and inversions. Subtelomeric imbalances are a significant cause of congenital disorders. Historically, screening for these abnormalities has utilized techniques such as GTG-banding analysis and fluorescence in situ hybridization (FISH) assays. CMA has proved to be useful in detecting segmental genomic copy variations in patients with global developmental delay, mental retardation, autism, multiple congenital anomalies and dysmorphism. It is also becoming a powerful tool in disease gene discovery, prenatal diagnostics, stillbirth, and cancer research. In a recent study published in Pediatrics, researchers from Baylor and Florida, USA reviewed results from 638 neonates with various birth defects. CMA was utilized to interrogate rearrangement–prone peri-centromeric and subtelomeric regions. Some 109 patients were identified with clinically significant abnormalities, most of which would not have been identified by karyotype analysis. Detection rates were 66.7% for "possible chromosomal abnormality" ± "other clinical indications”, 33.3% for ambiguous genitalia ± others, 27.1% for dysmorphic features + multiple congenital anomalies ± others, 24.6% for dysmorphic features ± others, 21.8% for congenital heart disease ± others, and 17.9% for multiple congenital anomalies ± others. In all, 16 patients had chromosomal aneuploidies, and 81 had segmental aneusomies including common microdeletion or microduplication syndromes and other genomic disorders. CMA appears to be a valuable clinical diagnostic tool that allows precise and rapid identification of genomic imbalances and mosaic abnormalities as the cause of birth defects in neonates however costs are currently fairly high (literature quotes $950 - $1500 per case).

Read more:
Pediatrics 2008; 122: 1310-18
Curr Opin Biotechnol 2008; 19: 36-40
Am J Med Genetics Part A; 146A: 2242-51