High resolution comparative genomic hybridisation in clinical cytogenetics

High resolution comparative genomic hybridisation (HR-CGH) is a diagnostic tool in our clinical cytogenetics laboratory. The present survey reports th e results of 253 clinical cases in which 47 abnormalities were detected. Am ong 144 dysmorphic and mentally retarded subjects with a normal conventiona l karyotype, 15 (10%) had small deletions or duplications, of which 11 were interstitial. In addition, a case of mosaic trisomy 9 was detected. Among 25 dysmorphic and mentally retarded subjects carrying apparently balanced d e novo translocations, four had deletions at translocation breakpoints and two had deletions elsewhere in the genome. Seventeen of 19 complex rearrang ements were clarified by HR-CGH. A small supernumerary marker chromosome oc curring with low frequency and the breakpoint of a mosaic r(18) case could not be clarified. Three of 19 other abnormalities could not be confirmed by HR-CGH. One was a Williams syndrome deletion and two were DiGeorge syndrom e deletions, which were apparently below the resolution of HR-CGH. However, we were able to confirm Angelman and Prader-Willi syndrome deletions, whic h are about 3-5 Mb. We conclude that HR-CGH should be used for the evaluati on of (1) dysmorphic and mentally retarded subjects where normal karyotypin g has failed to show abnormalities, (2) dysmorphic and mentally retarded su bjects carrying apparently balanced de novo translocations, (3) apparently balanced de novo, translocations detected prenatally, and (4) for clarifica tion of complex structural rearrangements.