Clinical utility of chromosomal microarray analysis.

Objective: To test the hypothesis that chromosomal microarray analysis frequently diagnoses conditions that require specific medical follow-up and that referring physicians respond appropriately to abnormal test results.

Methods: A total of 46,298 postnatal patients were tested by chromosomal microarray analysis for a variety of indications, most commonly intellectual disability/developmental delay, congenital anomalies, dysmorphic features, and neurobehavioral problems. The frequency of detection of abnormalities associated with actionable clinical features was tallied, and the rate of physician response to a subset of abnormal tests results was monitored.

Evaluation of chronic lymphocytic leukemia by oligonucleotide-based microarray analysis uncovers novel aberrations not detected by FISH or cytogenetic analysis.

Background: Cytogenetic evaluation is a key component of the diagnosis and prognosis of chronic lymphocytic leukemia (CLL). We performed oligonucleotide-based comparative genomic hybridization microarray analysis on 34 samples with CLL and known abnormal karyotypes previously determined by cytogenetics and/or fluorescence in situ hybridization (FISH).

Results: Using a custom designed microarray that targets >1800 genes involved in hematologic disease and other malignancies, we identified additional cryptic aberrations and novel findings in 59% of cases.

The clinical utility of enhanced subtelomeric coverage in array CGH.

Telomeric chromosome abnormalities are a substantial cause of mental retardation and birth defects. Although subtelomeric fluorescence in situ hybridization (FISH) probes have been widely used to identify submicroscopic telomeric rearrangements, array-based comparative genomic hybridization (array CGH) has emerged as a more efficient and comprehensive detection method. Due to the clinical relevance of telomeric abnormalities, it has been proposed that array CGH using panels of BAC clones that map to regularly spaced intervals along the length of each telomere could be used to characterize subtelomeric aberrations more precisely in a single experiment.

Development of a high-density pericentromeric region BAC clone set for the detection and characterization of small supernumerary marker chromosomes by array CGH.

Purpose: Small supernumerary marker chromosomes are centric chromosomal segments that, by definition, cannot be characterized unambiguously by conventional chromosome banding. Marker chromosomes are of particular interest in clinical cytogenetics because they are nearly 10 times more frequent in individuals with mental retardation (0.426%) than in the normal population (0.