Unexpected finding of a paternal premutation of the fragile X FMR1 gene in a female fetus of a premutation carrier mother.

We report on the fortuitous finding of a paternal premutation of the FMR1 gene during prenatal diagnosis in a female fetus whose mother was known to be a premutation carrier. Analysis of the DNA, extracted from cultured cells obtained by chorionic villus sampling, demonstrated the presence in the fetus of two FMR1 alleles of 23 and 71 CGG repeats, respectively. Chromosome analysis confirmed a normal female karyotype. The mother was known to be carrier of a normal allele of 23 repeats and a premutation of 79 repeats. Because the 23-CGG repeat allele is uncommon, we wanted to confirm its presence in the father, also given that a reduction in size from 79 to 71 repeats of the putative maternal allele is an unlikely event. Analysis of the father's DNA did in fact show that he is a carrier of a 69-CGG premutated allele. Therefore, the fetus inherited the normal 23-CGG allele from the mother and the 71-CGG allele from the father. Although a parental couple composed of two premutation carriers is rare, this case illustrates the importance of characterizing both parental genotypes when the results of prenatal diagnosis suggest an unusual segregation of the mutant and/or normal allele.