RESUMO
BACKGROUND: BAG3 gene mutations have been recently implicated as a novel cause of dilated cardiomyopathy (DCM). Our aim was to evaluate the prevalence of BAG3 mutations in Polish patients with DCM and to search for genotype-phenotype correlations. METHODS: We studied 90 unrelated probands by direct sequencing of BAG3 exons and splice sites. Large deletions/insertions were screened for by quantitative real time polymerase chain reaction (qPCR). RESULTS: We found 5 different mutations in 6 probands and a total of 21 mutations among their relatives: the known p.Glu455Lys mutation (2 families), 4 novel mutations: p.Gln353ArgfsX10 (c.1055delC), p.Gly379AlafsX45 (c.1135delG), p.Tyr451X (c.1353C>A) and a large deletion of 17,990 bp removing BAG3 exons 3-4. Analysis of mutation positive relatives of the probands from this study pooled with those previously reported showed higher DCM prevalence among those with missense vs. truncating mutations (OR = 8.33, P = 0.0058) as well as a difference in age at disease onset between the former and the latter in Kaplan-Meier survival analysis (P = 0.006). Clinical data from our study suggested that in BAG3 mutation carriers acute onset DCM with hemodynamic compromise may be triggered by infection. CONCLUSIONS: BAG3 point mutations and large deletions are relatively frequent cause of DCM. Delayed DCM onset associated with truncating vs. non-truncating mutations may be important for genetic counseling.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Cardiomiopatia Dilatada/genética , Genótipo , Mutação , Fenótipo , Sequência de Bases , Cardiomiopatia Dilatada/patologia , Primers do DNA , Éxons , Feminino , Humanos , Masculino , Linhagem , Polônia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Thoracic aortic aneurysm is often an asymptomatic but potentially lethal disease if its most catastrophic complication - aortic dissection - occurs. Thoracic aortic dissection is associated with a high mortality rate despite ongoing improvement in its management. We report a fatal outcome of thoracic aortic aneurysm in a male patient with bicuspid aortic valve. The patient was qualified for elective surgery of the ascending aorta and aortic valve at the age of 39 but he did not agree to undergo the proposed procedure. Three years later, he experienced acute aortic dissection and died despite a prompt diagnosis and complex management.