Prevalence of the FMR1 mutation in Taiwan assessed by large-scale screening of newborn boys and analysis of DXS548-FRAXAC1 haplotype.

If carrier women could be identified in time and take appropriate measures, fragile X syndrome (FXS) can be prevented. Wide screening of women to be or in their early pregnancy was considered a good approach to identify carriers without misdetection. Nevertheless, we argued against the cost-effectiveness of implementing such a screening program in Taiwan, due to the lower carrier rate found in our pilot study. To reliably estimate the prevalence of mutant FMR1 gene in Taiwan, we anonymously screened 10,046 newborn boys using bloodspot polymerase chain reaction (PCR). Among them, the sample from one boy, who was most likely had FXS, failed repeatedly in PCR amplification. The estimated prevalence of premutation (55-200 CGG repeats) and intermediate alleles (45-54 CGG repeats) was 1:1,674 (n = 6) and 1:143 (n = 70), respectively. All these estimates were constantly lower than that reported in Caucasian populations, with variable statistic significance. Furthermore, when comparing analyses of the distribution of alleles at the two most often investigated microsatellite loci, DXS548 and FRAXAC1, between 100 control and 28 unrelated fragile X chromosomes, we found no apparent founder haplotype prevalent among the fragile X patients. Because a few founder haplotypes were reportedly prevalent in two thirds of fragile X alleles in Caucasians and in Chinese from Central China, we thus suggested that lack of founder fragile X chromosomes might result in a relatively low prevalence of mutant FMR1 gene in a population, as observed in Taiwan.