Technological Advances in the Molecular Cytogenetic Diagnosis of Mental Retardation: Telomere Testing and Genome-wide Array Analysis

Accurate testing for chromosomal abnormalities is essential for elucidating the cytogenetic causes of mental retardation (MR). Major technological advances have been made in the molecular cytogenetic diagnosis of MR since G-banding analysis was first established in the early 1970s. The diagnostic yield in MR by G-banding has been estimated to be ∼5%. With the addition of telomere analysis, either by fluorescence in situ hybridization (FISH) or multiplex ligation-dependent probe amplification (MLPA), an additional 3–6% of patients have been found to have cytogenetic abnormalities as a cause of their MR. The implementation of targeted array comparative genomic hybridization (aCGH) drastically changed the efficiency of telomere testing and allowed a rapid transition to microarrays covering the whole genome for evaluating individuals with MR. Whole-genome microarray analysis has made a significant contribution to the molecular cytogenetic diagnosis of MR, increasing the diagnostic yield to over 15% in patients with MR. Although detection rates may vary, depending on the coverage and resolution of each array, this yield is still a significant increase compared to previous methodologies. Microarray analysis has revolutionized the contribution of clinical cytogenetics in defining the etiology of MR.