Final Report Summary - MVP-GEN (Genetics of mitral valve prolapse)
The heart chambers are separated by valves that open and close to let blood flow in only one direction. The mitral valve is located between the left atrium and the left ventricle. Failure of the mitral leaflets to close normally results in mitral valve prolapse (MVP). MVP is characterized by billowing of the mitral leaflets into the left atrium and is often accompanied by mitral regurgitation, which is blood flowing backward into the atrium. The valve leaflets are thickened and floppy. Serious complications can occur, including bacterial infections, arrhythmias, and even sudden death; MVP is the most common cause of mitral valve disorder requiring surgical repair. MVP is highly heritable; over 15% of patients with MVP report having relatives that are also affected. Using large families with many cases of MVP, three regions of the genome, or loci, have been identified that contain genes that cause MVP. The scientific purpose of this fellowship program was to identify genes in that are involved in the development of MVP. The identification and characterization of MVP genes is important to provide a starting point for understanding the molecular pathway that is important for valve development. This, in turn, may ultimately lead to therapeutic interventions designed to halt disease progression before serious complications develop.
The central hypothesis of this project was that gene mutation are disrupted in MVP patients, and that finding these mutations may help understand the biological pathways leading to myxomatous degeneration.
The Marie Currie MVP gen project is designed to establish a database and genetic bank of Israeli families segregating MVP and to use new advance DNA sequencing technology to clone these mutations and develop biological assays for further investigating their pathogenicity. We have allocated 19 MVP segregating families. Of these 2 were sent for genotyping. Two potential mutations segregating with MVP in these families were found. We are now working on validating these results. A second family was sequenced and a mutation in a gene important of EMT was found to be defective. The results in this family are being validated as well.
Throughout the years of the project, several advantages for the local community were reached. Two MD students joined the lab and had first hand opportunity to perform science. The use of genetic analysis, particularly of massive parallel sequencing for diagnosing of common cardiac disease, such as long QT and hypertrophic cardiomyopathy, became routine in our institution. Thus, the introduction of new genetic techniques benefits both science and clinical work in our institution.
The central hypothesis of this project was that gene mutation are disrupted in MVP patients, and that finding these mutations may help understand the biological pathways leading to myxomatous degeneration.
The Marie Currie MVP gen project is designed to establish a database and genetic bank of Israeli families segregating MVP and to use new advance DNA sequencing technology to clone these mutations and develop biological assays for further investigating their pathogenicity. We have allocated 19 MVP segregating families. Of these 2 were sent for genotyping. Two potential mutations segregating with MVP in these families were found. We are now working on validating these results. A second family was sequenced and a mutation in a gene important of EMT was found to be defective. The results in this family are being validated as well.
Throughout the years of the project, several advantages for the local community were reached. Two MD students joined the lab and had first hand opportunity to perform science. The use of genetic analysis, particularly of massive parallel sequencing for diagnosing of common cardiac disease, such as long QT and hypertrophic cardiomyopathy, became routine in our institution. Thus, the introduction of new genetic techniques benefits both science and clinical work in our institution.