RT Dissertation/Thesis
T1 Thoracic aortic aneurysms and dissections: genetic analysis of Mendelian and complex cases
A1 Gago Díaz, Marina
K1 Exome-wide association study
K1 Genetics
K1 Massive parallel sequencing
K1 Thoracic aortic aneurysms and dissections
AB The present doctoral thesis deals with the still partially unraveled genetic component of thoracic aortic aneurysms and dissections, a frequently asymptomatic but potentially lethal condition and major cause of sudden death. Our main objective was to contribute to further elucidate the genetics behind it, from both Mendelian and complex perspectives. We analyzed single and familial, forensic and clinical mendelian cases applying either a candidate-gene or whole exome massive parallel sequencing approach, respectively. We were able to solve approximately 23% of the forensic single cases and identified two strong candidate mutations in TGFB2 and PRKG1 genes in the two non-syndromic familial cases analyzed. For the analysis of complex cases we chose a population-based approach. We selected bicuspid aortic valve patients with and without concomitant thoracic aortic dilation and faced them against general population controls. We were not able to identify any consistently significant association, though a promising one arose involving HMCN2 and calcium metabolism that should be considered in future studies. The direct clinical consequences some of these results had supported molecular diagnosis, reliable genotype-phenotype correlations, and risk stratification as important tools for clinical management of these patients and family members at risk, as well as the need of research to continue.
YR 2017
FD 2017
LK http://hdl.handle.net/10347/15260
UL http://hdl.handle.net/10347/15260
LA eng
DS Minerva
RD 30 abr 2026