Prenatal Genetic Counseling on a Woman with Advanced Maternal Age and a Family History of a Known Genetic Disease

Carrier and prenatal diagnosis for families with known genetic disease are usually carried out by direct mutational analysis of the diseased gene if the mutations are known, or by an indirect method such as linkage analysis if the mutation is not identified. An alternative is the direct DNA sequencing of the entire diseases gene for mutations. Here we report a prenatal diagnosis of a woman with advanced maternal age who had an affected child with cystic fibrosis (CF) and unexpectedly revealed a fetus with trisomy 21 in the current pregnancy. The affected child was compound heterozygous for △F508 and an unidentified CF allele in the initial diagnosis. After much effort had been made to identify the unknown mutant allele and to find informative markers for linkage analysis, a rare mutation, Q207X, was eventually identified and a definitive diagnosis of CF for the subsequent pregnancy was possible. Unfortunately, the cytogenetic finding of a fetus with aneuploidy was so emotionally devastating that the pregnancy was terminated despite the absence of CF mutations. Although the occurrence of CF in Taiwan is rare, this case emphasizes the importance of thorough consideration of all factors that may affect pregnancy outcome during prenatal genetic counseling.