title: Mutation analysis of the phospholamban gene in 315 South Africans with dilated, hypertrophic, peripartum and arrhythmogenic right ventricular cardiomyopathies.
abstract: Cardiomyopathy is an important cause of heart failure in Sub-Saharan Africa, accounting for up to 30% of adult heart failure hospitalisations. This high prevalence poses a challenge in societies without access to resources and interventions essential for disease management. Over 80 genes have been implicated as a cause of cardiomyopathy. Mutations in the phospholamban (PLN) gene are associated with dilated cardiomyopathy (DCM) and severe heart failure. In Africa, the prevalence of PLN mutations in cardiomyopathy patients is unknown. Our aim was to screen 315 patients with arrhythmogenic right ventricular cardiomyopathy (n = 111), DCM (n = 95), hypertrophic cardiomyopathy (n = 40) and peripartum cardiomyopathy (n = 69) for disease-causing PLN mutations by high resolution melt analysis and DNA sequencing. We detected the previously reported PLN c.25C > T (p.R9C) mutation in a South African family with severe autosomal dominant DCM. Haplotype analysis revealed that this mutation occurred against a different haplotype background to that of the original North American family and was therefore unlikely to have been inherited from a common ancestor. No other mutations in PLN were detected (mutation prevalence = 0.2%). We conclude that PLN is a rare cause of cardiomyopathy in African patients. The PLN p.R9C mutation is not well-tolerated, emphasising the importance of this gene in cardiac function.
authors.affiliation: Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Old Groote Schuur Hospital, Groote Schuur Drive, Observatory, 7925, Cape Town, South Africa.
authors.forename: Maryam
authors.initials: M
authors.lastname: Fish
authors.affiliation: Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Old Groote Schuur Hospital, Groote Schuur Drive, Observatory, 7925, Cape Town, South Africa.
authors.forename: Gasnat
authors.initials: G
authors.lastname: Shaboodien
authors.affiliation: Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Old Groote Schuur Hospital, Groote Schuur Drive, Observatory, 7925, Cape Town, South Africa.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kraus
authors.affiliation: Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Old Groote Schuur Hospital, Groote Schuur Drive, Observatory, 7925, Cape Town, South Africa.
authors.forename: Karen
authors.initials: K
authors.lastname: Sliwa
authors.affiliation: Department of Genetics, Harvard Medical School, NRB 256, 77 Ave. Louis Pasteur, Boston, MA 02115, USA.|Division of Cardiovascular Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Seidman
authors.affiliation: Department of Genetics, Harvard Medical School, NRB 256, 77 Ave. Louis Pasteur, Boston, MA 02115, USA.|Division of Cardiovascular Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Burke
authors.affiliation: Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy.|Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Viale Golgi 19, 27100 Pavia, Italy.
authors.forename: Lia
authors.initials: L
authors.lastname: Crotti
authors.affiliation: Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Old Groote Schuur Hospital, Groote Schuur Drive, Observatory, 7925, Cape Town, South Africa.|Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy.|Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Viale Golgi 19, 27100 Pavia, Italy.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.affiliation: Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Old Groote Schuur Hospital, Groote Schuur Drive, Observatory, 7925, Cape Town, South Africa.
authors.forename: Bongani M
authors.initials: BM
authors.lastname: Mayosi
mesh_terms: D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics*; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D058725:Peripartum Period; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000175:diagnosis / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013019:South Africa; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D000099211:Phospholamban