Increased frequency of the MTHFR A1298C mutation in an Irish population.

To the Editor: We would like to thank Drs. Allen and Chiafari for their comments. They reiterate many of the points we made in our report (1 ). We are glad that they also had similar findings. However, they suggest that we differ in the detection of polymorphisms. In the Discussion section of our report (1 ), we speculated that our cutoff score might be too high because we observed that a polymorphism in exon 6 had a score of 6. In their study, the GeneChip detected one of six exon 4 (codon 72) polymorphisms, whereas we were unable to detect any in 12 cases from which we obtained a PCR product. We would argue that this was not a significant difference because both sample sizes are small. In fact, it actually supports our conclusion that a combination of both microarray and sequencing is required to identify p53 alterations, as they would have missed five polymorphisms. We also look forward to being able to use the next-generation p53 microarray, as we stated in our report (1 ), because this methodology definitely has a role to play in sequencing of the p53 gene.