Mosaicism for a full mutation and a normal size allele in two fragile X males

Confirmation of the clinical diagnosis of fragile X syndrome by molecular tests is based on both the presence of a full mutation and methylation of the promotor region of the FMR1 gene. The mechanism leading to mosaic alleles of repeat number and the role of methylation in this process is still under discussion. We report two cases of males who show mosaic patterns for both number of CGG repeats and methylation status. In the first patient, a mosaic pattern of a normal allele of 34+/-1 CGGs, a borderline premutation/full mutation, and a full mutation was observed. The mother exhibited alleles of 30+/-1 and approximately 100 CGGs. The second patient was mosaic for a normal allele of 47+/-1 CGGs and a full mutation. His mother carried alleles of 40+/-1 and approximately 100 CGGs. Chromosomal analysis in the patients showed normal male karyotypes with no evidence that they had inherited both maternal X chromosomes. Furthermore, haplotyping excluded disomy of the repeat flanking region in these patients. So far, it is not clear whether the normal alleles in the patients, leukocytes of 34 and 47 CGGs, respectively, may be caused by the contraction of the maternal premutations of 100 CGGs or be caused by the deletion from the full mutation alleles.