Evaluation of a mutation screening strategy for sporadic cases of ATR-X syndrome

We report on the evaluation of a strategy for screening for XNP/ATR-X mutat ions in males with mental retardation and associated dysmorphology. Because nearly half of the mutations in this gene reported to date fall into a sho rt 300 bp region of the transcript, we decided to focus in this region and to extend the mutation analysis to cases with a negative family history. Th is study includes 21 mentally retarded male patients selected because they had severe mental retardation and a typical facial appearance. The presence of haemoglobin H or urogenital abnormalities was not considered critical f or inclusion in this study. We have identified six mutations which represen ts a mutation detection rate of 28%. This figure is high enough for us to p ropose this strategy as a valid first level of screening in a selected subs et of males with mental retardation. This approach is simple, does not requ ire RNA preparation, does not involve time consuming mutation detection met hods, and can thus be applied to a large number of patients at a low cost i n any given laboratory.