Failure to find amplified product by PCR analysis in such a case could mean that the fetus is not affected, or that there is a full mutation that is too large to be detected by PCR. The next logical step is a Southern blot analysis of genomic DNA from fetal cells. Routine karyotyping of the amniotic fluid cells is much less sensitive than a Southern blot analysis. Karyotyping of the unaffected father cannot provide information about the status of the FMR1 gene in the fetus because amplification of the trinucleotide occurs during oogenesis. For the same reason, PCR analysis of the mother's FMR1 gene is of no value.