Prenatal diagnosis of Marfan syndrome: identification of a fibrillin-1 mutation in chorionic villus sample.

Marfan syndrome (MFS) is one of the most common heritable connective tissue disorders and is caused by mutations in a gene coding for fibrillin-1. All but one of over 30 published mutations have been unique and specific prenatal diagnostics can only be provided to families with a previously established mutation. We have earlier identified a 366 bp deletion of fibrillin mRNA in a three-generation British Marfan family. An affected female in the family together with her husband sought prenatal diagnosis. Chorionic villus sampling was performed at 11.5 weeks of gestation and total RNA was directly extracted from the sample. After reverse transcription and polymerase chain reaction (PCR) of the cDNA, the same deletion was identified in the chorionic villus sample (CVS) and the mother's sample in agarose gel electrophoresis. The fetal origin of the CVS was confirmed with polymorphic markers. In addition to the mutation analysis, CVS cells of the proband and a control fetus were cultured for biochemical studies of fibrillin polypeptides. The results of the biochemical investigation were in concordance with the molecular analysis.