Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Aortic aneurysm, familial thoracic 3 (AAT3) [I71.1] [I71.2]

OMIM numbers: 610168, 190182 (TGFBR2)

Dr. rer. nat. Karin Mayer

Scientific Background

In 2003 the third gene locus for familial TAAD (TAAD2) was mapped on chromosome 3p24–25. This region overlaps with the second gene locus for Marfan syndrome (MFS2) which was detected in 1993. A mutation analysis of the TGFBR2 (transforming growth factor beta receptor 2) gene in 2004 showed that the gene locus TAAD2 is allelic to TGFBR2. At present, it is called AAT3.

In a study from Pannu et al. (2005) four of 80 families (5%) with familial TAAD were diagnosed with a mutation in TGFBR2 that always led to a change of the amino acid arginin in position 460 of the protein. This highly conserved position seems to exhibit a predilection site for mutations for familial TAAD. Although these mutations are also located in the cytoplasmatic serin/threonin kinase domain of TGFBR2, they have not been associated with Marfan-like syndromes and Loeys-Dietz syndrome so far. In total, mutations in TGFBR2 have been identified in 4% of patients with isolated TAAD and a positive family history.