In most families, direct testing is the only approach available since appropriate family members for linkage analysis are not available. When a mutation is detected in an individual, it must be combined with the available clinical data, and potentially with testing of other family members, to establish a diagnosis. At the H.A. Chapman Institute, nearly all of the patients with an identified  mutation to date have also had serious life-threatening heart complications. Therefore, detecting a Marfan syndrome mutation within a family, can allow relatives with or without clear symptoms, to determine their risk of the disease, and may be beneficial to relatives who might otherwise remain unaware of their need for cardiologic testing or monitoring.

Testing Methodology:

The entire Fibrillin 1 gene (roughly 9,000 nucleotides) is sequenced, using mRNA extracted from live fibroblasts. The mRNA is the starting material of choice, since it allows for the identification of splicing mutations and exon deletions, which account for  approximately 20% of all Marfan syndrome mutations. These splicing mutations and exon deletions are NOT detectable by traditional sequencing of genomic DNA. Sequencing of the mRNA is currently the most accurate, and thorough method of mutation detection.

In classical Marfan syndrome patients, this approach will detect a mutation in roughly 90% of individuals. In patients with non-classical Marfan, the detection rate may be much lower. In the case of patients with no family history, and who do not meet the full Ghent criterion, the detection rate may range from 30-50%. Thus, the detection of a mutation can be very helpful in establishing a diagnosis; but the absence of a mutation can not rule out Marfan syndrome. The significance of a negative result in these non-classical Marfan patients is ambiguous.