Work on the hereditary disorders of connective tissues predominately focuses on Marfan syndrome and related disorders. Though the skeletal dysplasias can be considered disorders of connective tissue, these disorders are covered under other projects. A total of 126 patients with Marfan syndrome and related conditions (MASS phenotype, mitral valve prolapse syndrome, familial aortic dissection) were seen in the NCHGR Genetics Clinic. Clinical data collected included detailed information on skeletal, ocular and cardiovascular manifestations in each patient. Eventually, the plan is to correlate clinical observations with specific mutations in the fibrillin-1 (FBN1) gene. Additionally, clinical data will be analyzed to assess the validity of proposed new diagnostic criteria for Marfan syndrome. Long-term clinical follow-up is planned for patients not fulfilling the diagnostic criteria, to determine the natural history of these patients and also the optimal management scheme for them. Using a panel of 65 PCR primer pairs, we screened genomic DNA from 11 Marfan syndrome patients to identify mutations in the fibrillin (FBN1) gene. Analysis of amplified PCR products yielded 33 heteroduplexes. Mutations in the fibrillin gene were characterized in three patients. A collaborative effort is underway with Dr. H Dietz at Johns Hopkins University to develop a more rapid means of mutation detection in the FBN1 gene. These results and similar analysis will allow us to search for genotype: phenotype correlations in this phenotypically heterogeneous condition.
