Molecular Diagnosis of the FBN1 Gene and Phenotype-Genotype Analysis in Taiwanese Patients with Marfan Syndrome
Date Issued
2009
Date
2009
Author(s)
Cheng, Hui-Yu
Abstract
Marfan syndrome is an autosomal dominant inheritance disorder with multisystem connective tissue involvement. The recognized features include cardiovascular, skeletal, and ocular systems; about 70% patients die from cardiovascular complications, and mainly aortic dissection. The in-hospital mortality rate of Marfan patients with dissection is about 21%. Deceasing the possibility of sudden death is the most essential mission for Marfan patients, and using the medicine to prevent/ delay process of the aorta being dilated, even doing the preventive operation before the aorta comes to be dissection. Molecular genetic testing of the FBN1 (Fibrilin-1) gene, the target gene known to be associated with Marfan syndrome, could detect 70 ~ 93% of mutations. Due to the heterogenous clinical manifestations and genetic background, a more sophisticated integration on clinical support including genetic counseling and genetic diagnosis is still warrant. Due to the purpose above, we use high resolution melting (HRM), Automatic sequencing and multiplex ligation-dependent probe amplification (MLPA) to evaluate FBN1 mutations for clinical diagnosing Marfan patients in 2005 ~ 2009. Besides, we set the special clinic to collect the clinical symptom for Marfan patients in National Taiwan University Hospital since 2008. We had screened 157 individual families that 20 % (31/157) cases with family history and identified 58 different mutation (two cases from different family with the same mutation). The detection rate is about 37% (59/157). When family history was taken into consideration, the mutation detection rate rose to 90 % (28/31). We further investigated the phenotypic data and found that 32 % (50/157) cases fit the Ghent criteria for Marfan syndrome, then the detection rate which fitting to criteria rose to 98% (49/50). Therefore, we firmly believe the importance of genetic testing, Ghent criteria and family history to diagnose Marfan syndrome. If we could check every symptom according to Ghent criteria, make the family history much more clear and combine with gene diagnosis, we could not only diagnose Marfan syndrome more explicitly but also enhance the detection ratio more accurately. By combining with the setting of special clinic, genetic diagnosis and comphresive genetic counseling, it is promising that we could provide a better integrated clinical service for Marfan patients, and to have further discovery and achievement in genotype-phenotype correlations to put in use of future treatments and expect to establish greater and more integrated database as well.
Subjects
Marfan syndrome
Fibrilin-1
Ghent criteria
Detection rate
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