Bibliographic Details
| Title: |
SMAD3pathogenic variants: risk for thoracic aortic disease and associated complications from the Montalcino Aortic Consortium |
| Authors: |
Hostetler, Ellen M, Regalado, Ellen S, Guo, Dong-Chuan, Hanna, Nadine, Arnaud, Pauline, Muiño-Mosquera, Laura, Callewaert, Bert Louis, Lee, Kwanghyuk, Leal, Suzanne M, Wallace, Stephanie E, Rideout, Andrea L, Dyack, Sarah, Aatre, Rajani D, Boileau, Catherine, De Backer, Julie, Jondeau, Guillaume, Milewicz, Dianna M |
| Source: |
Journal of Medical Genetics (JMG); 2019, Vol. 56 Issue: 4 p252-260, 9p |
| Abstract: |
BackgroundPathogenic variants in SMAD3cause thoracic aortic aneurysms and dissections, along with aneurysms and rupture of other arteries. Here, we examined differences in clinical presentation of aortic events (dissection or surgical repair of an aneurysm) with respect to age and variant type in an international cohort of individuals with SMAD3variants.MethodsAortic status and events, vital status and clinical features were abstracted through retrospective review of medical records of 212 individuals with 51 unique SMAD3variants, including haploinsufficiency (HI) and missense substitutions in the MH2 domain, as well as novel in-frame deletions and missense variants in the MH1 domain.ResultsAortic events were documented in 37% of cases, with dissections accounting for 70% of events. The median age at first aortic event was significantly lower in individuals with SMAD3MH2 missense variants than those with HI variants (42years vs 49 years; p=0.003), but there was no difference in frequency of aortic events by variant type. The cumulative risk of an aortic event was 50% at 54 years of age. No aortic events in childhood were observed.ConclusionsSMAD3pathogenic variants cause thoracic aortic aneurysms and dissections in the majority of individuals with variable age of onset and reduced penetrance. Of the covariates examined, the type of underlying SMAD3variant was responsible for some of this variation. Later onset of aortic events and the absence of aortic events in children associated with SMAD3variants support gene-specific management of this disorder. |
| Database: |
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