Human Genome Research Project

Marfan Research Group

• Head of Unit
• Summary of Unit
• Goals of Unit

Head of Unit

Summary of Unit

The Marfan Research Group provides a research and diagnostic facility for the screening of the FBN1 gene in patients referred with a possible diagnosis of Marfan syndrome, or a Marfan-related condition. We have studied more than 600 individuals from approximately 260 families. A total of 85 FBN1 gene mutations have been characterised. We currently use a DHPLC approach and have been investigating the usefulness of MLPA in FBN1 mutation negative patients who may have a large FBN1 insertion or deletion. The group's success in FBN1 gene mutation detection rivals those of international groups. The methodology allows for detection of single base substitutions, deletions and insertions. Mutation detection is 85% for those who meet the Ghent diagnostic criteria for Marfan syndrome, and 25% in those who do not. We have developed a Marfan database that incorporates clinical and molecular data, links to the international databases and allows for powerful statistical analyses and genotype-phenotype correlations. With the advent of new knowledge, the MRG has extended its research interests to include a new group of disorders, the TGFB-signallopathies. Recent research has included DHPLC of the TGFBR1 and TGFBR2 genes, wherein we have detected mutations in patients with an “extended” Marfan phenotype (Furlong syndrome, possible Lujan-Fryns syndrome and Loeys-Dietz syndrome). We have strong collaborative links with international groups involved in the study of aortic aneurysms and dissections, arterial tortuosity syndromes, bicuspid aortic valve disease and the TGFB signalling pathway. We regularly contribute data to the International Marfan Database. We have participated in a “hybrid” documentary on Marfan syndrome, “Jabe Babe”, short-listed at the 2005 Cannes Film Festival, and nominated for three AFI and one IF award.

Goals of Unit

Our goals are to:

• Educate physicians and the community about Marfan syndrome
• Maintain a high FBN1 mutation detection rate
• Establish genotype-phenotype correlations in Marfan syndrome
• Discover the disease pathogenesis in individuals who are FBN1 mutation negative
• Establish mutation screening for the TGFBR1 and TGFBR2 genes
• Become the National Reference Laboratory in Australasia for Marfan syndrome and related disorders