Comment on Gialluisi et al

摘要

As authors of the first paper describing the methodology used by Gialluisi et al in their paper on the high allele frequency for Wilson disease in the Sardinian population, we want to congratulate them with their result. The paper clearly shows the strength of this methodology. We were also particularly impressed by their conscientious approach to determine the inbreeding coefficient in this special population. Still we want to draw attention to some inaccuracies in their paper, which-in our opinion-should be avoided by future users of this method, as they may result in underestimation of the gene frequency - ie, the total pathogenic allele frequency-and birth prevalence of the disorder. First of all, the authors disregard 14 mutations with relative frequencies below 1%. By including these, the gene frequency becomes 0.0195, instead of 0.0191. Second, the authors included only patients with unambiguous genotype and detailed geographical provenance of parents. However, leaving out seemingly heterozygous patients with a second, unidentified mutation will have the same effect on the estimation of the gene frequency as disregarding known mutations.