ABSENCE OF FMR-1 GENE-EXPRESSION CAN BE DETECTED WITH RNA EXTRACTED FROM DRIED BLOOD SPECIMENS

Fragile X syndrome is a genetic disorder caused by abnormal function o f the FMR-1 gene. The majority of fragile X syndrome patients carry an expansion of the CGG tri-nucleotide repeat in the FMR-1 gene, whereas others have a deletion or a point mutation in the FMR-1 structural ge ne. Ln this report, we analyzed a typical family with three male patie nts. RNA from Epstein-Barr virus transformed lymphoblastoid cells was used for RNase protection as say and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Five normal individuals and one asym ptomatic heterozygote from this family expressed detectable FMR-1 tran scripts, whereas three fragile X patients showed no sign of expression with either assay. To extend the application of this PCR-based assay to laboratory diagnosis of fragile X syndrome, we confirmed that dried blood samples collected on screening filter papers for newborns are a n adequate source of RNA for RT-PCR. Moreover, fragile X patients from the study family and another family were reliably identified by the a bsence of the FMR-1-specific PCR product from the dried blood specimen s. Our studies indicate that this simple assay can be used to diagnose the fragile X syndrome for the majority of male patients.