Jt. Pai et al., ABSENCE OF FMR-1 GENE-EXPRESSION CAN BE DETECTED WITH RNA EXTRACTED FROM DRIED BLOOD SPECIMENS, Human genetics, 93(5), 1994, pp. 488-493
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.