Feasibility of blood spot PCR in large-scale screening of fragile X syndrome in southern Taiwan.
OBJECTIVE
Fragile X syndrome (FXS) is the most common form of hereditary mental retardation. Early diagnosis of the disease may lead to better prognosis for children who participate in early intervention programs. This study attempted to evaluate whether screening newborn boys with simple polymerase chain reaction (PCR) assay could be an effective approach for detection of mutation carriers and FXS, a process that may also facilitate detection of young carrier mothers.


METHODS
Filter paper blood spot samples of 4843 newborn boys were collected from five hospitals in southern Taiwan. They were tested with a simple non-radioactive PCR for the presence of FMR1 gene mutation by determining the number of FMR1 CGG repeats. By this method, the examined sample can be reliably classified as normal (<40), intermediate (40-54), and mutant group (> 54), according to the number of CGG repeats.


RESULTS
The FMR1 CGC repeat number of all but four samples was below 54, with 90 samples (1.8%) between 40 and 54 (the intermediate range). Two of the four abnormal samples were carriers of the premutation. The other two failed repeatedly in PCR amplification for the FMR1 gene, but not for the control K-ras gene. Hence, these samples seemed to be candidate carriers of large premutation or even full mutation, indicating the need for confirmation with standard Southern blot analysis.


CONCLUSIONS
This study demonstrated that a simple PCR combined with blood spot sampling is effective and feasible for large-scale screening of newborn boys for fragile X carrier status. The relatively low carrier rate in this population suggests that the cost-effectiveness of implementation of such screening on a population-wide basis would be lower than in the Jewish and Caucasian populations.
Chow
Julie Chi
JC
Department of Pediatrics, Chi-Mei Foundation Hospital, Tainan, Taiwan.
Chen
De-Jen
DJ
Lin
Ching-Nan
CN
Chiu
Chin-Yang
CY
Huang
Chung-Bin
CB
Chiu
Pao-Ching
PC
Lin
Chi-Ho
CH
Lin
Shio-Jean
SJ
Tzeng
Ching-Cherng
CC
D004247:DNA / Q000097:blood; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D016601:RNA-Binding Proteins; D013624:Taiwan / Q000453:epidemiology
D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human