Molekulargenetische studien bikuspider aortenklappen

Background: Bicuspid aortic valve (BAV), the most common congenital cardiac malformation, is caused by fusion of valve cushions at the onset of valvulogenesis. Although its exact pathogenesis is still unclear, a genetic basis appears more and more likely. Search for a potential candidate gene by reviewing semilunar valve morphogenesis led to the Ubiquitin Fusion Degradation 1 Like (UFD1L) gene, which is highly expressed in the cardiac outflow tract during embryogenesis. Methods: Aortic valves were collected during surgery from 39 patients with BAV (mean age 56.8±18.1 years, group A) and from 38 patients with tricuspid aortic valves (TAV) (mean age 61.7±16.1 years, group B). Fluorescence in situ hybridisation was performed for detection of microdeletion, quantitative reverse transcription polymerase chain reaction to measure gene expression, and Western blot to analyze the amount of Ufd1l protein. Results: No microdeletion was found in either group in the critical region of chromosome 22 containing the UFD1L gene. UFD1L gene expression, however, was significantly reduced in BAV (median: 787-fold) compared with TAV (median: 10887-fold, p=0.001). The amount of Ufd1l protein was also significantly diminished in BAV (3.9±2.6 vs. 8.4±4.8 optical density; p<0.05). Conclusions: BAV was associated with downregulation of UFD1L gene expression, supporting the hypothesis that BAV is a genetic disorder with the UFD1L gene as one potential candidate gene warranting further investigation.