OBJECTIVE: It has been firmly established that mutations in the gene for 
fibrillin 1, FBN1, cause Marfan syndrome (MFS). FBN1 mutations can also cause 
other phenotypes, such as ectopia lentis (EL) and familial isolated thoracic 
aortic aneurysm and dissection (FAA). When the clinical presentation is typical, 
diagnosis of MFS is usually easy to make. However, there can be a marked 
phenotypic variation between affected subjects even in one family, and making 
the diagnosis can be challenging, especially in childhood. The objective of this 
study was to test the sensitivity of conformation sensitive gel electrophoresis 
(CSGE) for detecting mutations in FBN1 in MFS and related phenotypes.
DESIGN: Setting up CSGE analysis for the FBN1 gene and testing the method first 
by screening coded samples from 17 MFS patients with previously detected FBN1 
mutations. We then used a test set consisting of 46 coded samples representing 
MFS, related phenotypes, and controls.
RESULTS: Sixteen of the 17 known mutations were detected. Altogether 23 
mutations were detected in a test set consisting of 46 coded samples 
representing MFS, related phenotypes, and controls. Nineteen of the mutations 
were novel. The mutation was detected in 18 of the 20 MFS patients and in one 
patient with familial EL, but not in a patient with sporadic MASS syndrome, any 
of the five sporadic annuloaortic ectasia (AAE) patients, or any of the 15 
controls. A FBN1 mutation was detected in four members of a multigeneration 
family with AAE, however.
CONCLUSIONS: These results indicate that CSGE is highly sensitive for the 
detection of mutations in FBN1, and that molecular diagnostics is a useful means 
of confirming clinical diagnoses of MFS and related disorders. Further careful 
investigations are needed, however, in order to correlate the interfamilial and 
intrafamilial clinical variabilities of fibrillinopathies and mutations in FBN1.