CGH microarray studies in idiopathic developmental/ cognitive impairment: association of historical and clinical features and the De Vries Score

摘要

Objective. Studies have confirmed that copy number variations(CNV) in the human genome contribute to the etiology of mentalretardation/ development delay/ congenital anomalies. We soughtto evaluate the use of a microarray in the context of a clinical geneticspractice, to determine if there were any specific clinical findingsthat predict the discovery of a CNV. Patients and methods. 334 caseswith idiopathic mental retardation/impairment/development delay/disability or a combination of these findings were studied using arraycomparative genomic hybridization (Signature Chip Version 4). Thesubjects had previously had a non diagnostic medical genetics evaluation.Clinical findings were collated by a chart review. Each patientwas scored according to a previously published clinical checklist by deVries and colleagues. Results. Of 334 patients, 8 were excluded due toa syndromic diagnosis being established by clinical and/or microarraytesting. Out of the remaining 326 patients, 33 (10%) showed CNVs,of which 5 were maternally inherited, 4 paternally inherited, 11 werede novo, and the origin of 13 remained unknown. The mean de Vriesscore was greater in the CNV group than in the non CNV group (4.17and 3.95, respectively). No patient in the CNV group had a score ofless than 3, while in the non CNV group, 12% of patients had scoresless than 3. Conclusions. The De Vries clinical score was higher inCNV cases compared to those with no CNV (p=0.04) but this differenceis unlikely to be clinically meaningful. Several features reachedstatistical significance of p<0.05 but we were unable to delineate patternsof features that might increase the yield of positive CNV results.