Array CGH in the routine diagnostic work-up of mental retardation

Array comparative genomic hybridization (CGH) analysis has become an essential part of the diagnostic work-up of mental retardation in children. Using bacterial artificial chromosome (BAC)-array CGH, a follow-up examination on chromosomally inconspicuous children with mental retardation (n=194) revealed a chromosomal imbalance as the cause of the retardation in 17 patients (9%). In a small pilot study on 10 patients, we could demonstrate the benefit of applying a second, oligonucleotide-based array CGH platform as a reliable and rapid validation tool for ambiguous CGH results, in particular if duplications were suspected (cross-validation). Based on our own experience and that of other groups, a stepwise approach for the diagnosis of mental retardation in children involving a combination of BAC- and oligonucleotide-array CGH as well as fluorescence in situ hybridization (FISH) is recommended.