Genetics Associates is proud to announce that array comparative genomic hybridization (aCGH) testing is available on a research basis at our laboratory. aCGH, also called microarray analysis, is a new molecular cytogenetic technology that evaluates areas of the human genome for gains or losses of chromosome segments at a higher resolution than traditional karyotyping. The test targets areas of the human genome that, when deleted or duplicated, are known or highly suspected to cause well-characterized genetic conditions with mental disabilities and/or birth defects including loci of known microdeletion/microduplication syndromes, subtelomeric regions, and pericentromeric regions. Due to the small size, many of these DNA imbalances may not be detected by standard cytogenetics. Array CGH will also identify marker chromosomes, some cases of mosaicism, and aneuploidy. The American College of Medical Genetics includes aCGH as an adjunct to standard cytogenetics for patients with developmental delay (DD) or mental disabilities (MD) when no chromosomal or molecular cytogenetic abnormalities are detected and the results of fragile X testing are negative. Recent studies indicate that MD/DD-targeted CGH-based assays can detect clinically relevant genomic alterations in roughly 5.6% to 11% of patients with idiopathic developmental conditions.

A microarray slide contains thousands of different copies of DNA sequences attached to a glass slide in an organized fashion or array. Fluorescently labeled DNA from both patient and a normal control are applied to the slide and compete to attach or hybridize to their corresponding DNA segments. Computer software analyzes the fluorescent signals for areas of unequal hybridization of patient versus control DNA, signifying a DNA dosage alteration (deletion or duplication). Any abnormal finding is verified by FISH visualization, which is essential for accurate diagnosis and recurrence risk estimation. The performance characteristics of this test, including sensitivity and specificity, have been determined by Genetics Associates, Inc. All results are interpreted by the board certified and Tennessee licensed cytogenetics directors at our laboratory who, are available to discuss results and offer clinical advice.

Appropriate candidates for this testing are patients who have: mental disability of unknown etiology; autism; congenital anomalies; dysmorphic features; a suspected syndrome with normal chromosomes/subtelomere. The required specimen type is 5-7 mL peripheral blood collected in a sodium heparin tube. Complete patient demographic and clinical information is required to insure that the most appropriate testing is performed.

Limitations of array CGH are as follows: balanced chromosome rearrangements; balanced inversions; alterations in chromosome structure at areas of the genome not covered by the array; sequence alterations or single-base pair mutations; mosaicism at a level lower than 20%; some types of polyploidy, such as triploidy.