An effective strategy of using molecular testing to screen mentally retarded individuals for fragile X syndrome

Fragile X syndrome (FXS) is the most common form of familial mental retarda tion (MR). It is caused by the expansion of the CGG repeat in the FMR1 gene on the X chromosome. To date, FXS is not treatable, but can be prevented b y prenatal genetic examination. Identifying women who carry a full mutation or premutation FMR1 gene is thus very important, and can be done by tracin g family members of FXS subjects. However, most of the FXS subjects in Taiw an as well as those in many other countries have not been identified. In th is study the authors attempt to develop reliable and inexpensive tests suit able for a large-scale screen of subjects with MR for FXS. Together with th eir previous study, a total of 311 male and 160 female subjects with MR wer e screened with nonradioactive Southern blot assay using mixed deoxyribonuc leic acid from three subjects of the same sex. From these subjects, nine ma le subjects and one female FXS subject were diagnosed. All male subjects we re also screened with nonradioactive polymerase chain reaction (PCR). These nine male FXS subjects were also detected on the basis of PCR amplificatio n failure. No false-negative results were discerned. The PCR procedure was simplified further by combining it with an analysis of a blood spot on filt er paper, which is a much simpler and cheaper method for sample collection and DNA preparation. This method was then used to screen 104 boys with MR. Two of them were suspected, and later confirmed with Southern blot assay, a s subjects with FXS. This study suggests that simple PCR combined with bloo d spot analysis could be a reliable, inexpensive test that is feasible for a large-scale screening of male subjects with MR for FXS. However, Southern blot assay with mixed deoxyribonucleic acid is appropriate for screening f emale subjects. Based on this strategy, most FXS subjects could be identifi ed easily for further management.