Genomic imbalances are considered the most frequent causes of mental retardation (MR). Although widespread screening with novel molecular karyotyping methods, such as multiplex ligation-dependent probe amplification (MLPA) and array-based comparative genomic hybridization (Array- CGH) might be desirable, effective clinical preselection is essential because of the technical complexities and cost of testing. This study focuses on a retrospective analysis of clinical features in patients with MR of unknown etiology, thereby assessing the sensitivity of a six item checklist in identifying rearranged subjects. The diagnostic powers of single techniques were also evaluated. We studied 164 subjects with MR who had completed the follow diagnostic process: karyotype and eventually fluorescence in situ hybridization (FISH) in case of suspected microdeletion syndrome, specific analysis in case of suspected X-linked or monogenic disease, MLPA for subtelomeric rearrangements in patients negative to previous tests, Array-CGH in patients negative to MLPA. A six items checklist based on relevant clinical signs was retrospectively applied. 5 patients were carrier of chromosomal abnormalities (3 detected by karyotype and 2 by FISH), 3 were affected by X-fragile syndrome, 6 had mutations, and 33 were carriers of genomic imbalances (9 detected by MLPA and 24 by Array-CGH), while 117 resulted negative to any tests. In patients with genomic imbalances and in subjects without rearrangements the median score of the checklist was 6 (range 3-9) and 4 (range 0-8), respectively (P <0,0001). The ROC analysis for the diagnostic accuracy of our checklist showed an area under the curve of 0.74 (95% confidence interval: 0.65-0.83). Using a cut-off for the score of U3, 24% of patients could have been excluded without missing any genomic imbalances. This study supports the evidence that the application of a clinical checklist may improve the rate of pathological findings in patients with MR.
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