bav with aortic aneurysm linked to chromosone 15q
bav with aortic aneurysm linked to chromosone 15q
Here's another interesting article below .... this one from the American Journal of Human Genetics and by distinquished researchers. Indeed, genetic factors contribute to the development of thoracic aortic aneurysms and bav.
Linkage of Familial Bicuspid Aortic Valve with Aortic Aneurysm to Chromosome 15q. D.L. Goh1,2, L.F Han1, D.P. Judge1, J.A. Geutbner1, I. McIntosh1, A. Patel3, G.H. Thomas3, C.T. Basson4, D.M. Milewicz5, H.C. Dietz1,6. 1) Johns Hopkins University School of Medicine, Baltimore, MD; 2) National University of Singapore, Singapore; 3) Kennedy Krieger Institute, Baltimore, MD; 4) Weill Medical College of Cornell University, New York, NY; 5) University of Texas-Houston Medical School, Houston, TX; 6) Howard Hughes Medical Institute.
Bicuspid aortic valve (BAV) is the most common congenital heart malformation, with an estimated incidence of 1%. BAV can be associated with ascending aortic aneurysm (AscAA), historically attributed to hemodynamic perturbation caused by valve malformation. Comprehensive evaluation of multiple pedigrees segregating BAV with AscAA revealed a high incidence of individuals with AscAA alone, suggesting that BAV and AscAA are both primary manifestations of a single gene defect with variable expression. BAV/AscAA segregates as an autosomal dominant trait with incomplete penetrance and wide variation in the age of onset of aortic enlargement, ranging from infancy to mid-adult life. Maximal enlargement of the aorta frequently occurs above the sinotubular junction, distinguishing BAV/AscAA from Marfan syndrome or previously reported forms of familial AscAA. We identified a patient with multiple congenital anomalies that included BAV, AscAA, sensorineural hearing loss, growth failure, developmental delay and dysmorphic facies. This was associated with a de novointerstitial deletion [46,XX,del(15)(q25q26.1)] spanning 7Mb, as mapped by FISH and loss of heterozygosity. This suggested that a gene for BAV/AscAA maps within this critical interval. Ten multiplex families segregating BAV/AscAA were genotyped with polymorphic markers spanning the deleted interval and nine were consistent with linkage to this region of chromosome 15q with a maximum single-point LOD score of 3.60. These data mandate periodic echocardiographic follow-up of all first-degree relatives of individuals with BAV/AscAA including those without valve malformation. Further refinement of this locus and identification of the gene(s) responsible for BAV/AscAA will allow molecular assignment of risk and provide important insight regarding the molecular determinants of aortic wall homeostasis.
