title: Clinical features, spectrum of causal genetic mutations and outcome of hypertrophic cardiomyopathy in South Africans.
abstract: BACKGROUND
  Little is known about the clinical characteristics, spectrum of causal genetic mutations and outcome of hypertrophic cardiomyopathy (HCM) in Africans. The objective of this study was to delineate the clinical and genetic features and outcome of HCM in African patients.
  
  
  METHODS
  Information on clinical presentation, electrocardiographic and echocardiographic findings, and outcome of cases with HCM was collected from the Cardiac Clinic at Groote Schuur Hospital over a mean duration of follow up of 9.1 ± 3.4 years. Genomic DNA was screened for mutations in 15 genes that cause HCM, i.e. cardiac myosin-binding protein C (MYBPC3), cardiac β-myosin heavy chain (MYH7), cardiac troponin T2 (TNNT2), cardiac troponin I (TNNI3), regulatory light chain of myosin (MYL2), essential light chain of myosin (MYL3), tropomyosin 1 (TPM1), phospholamban (PLN), α-actin (ACTC1), cysteine and glycine-rich protein 3 (CSRP3), AMP-activated protein kinase (PRKAG2), α-galactosidase (GLA), four-and-a-half LIM domains 1 (FHL1), lamin A/C (LMNA) and lysosome-associated membrane protein 2 (LAMP2). Survival and its predictors were analysed using the Kaplan-Meier and Cox proportional hazards regression methods, respectively.
  
  
  RESULTS
  Forty-three consecutive patients [mean age 38.5 ± 14.3 years; 25 (58.1%) male; and 13 (30.2%) black African] were prospectively enrolled in the study from January 1996 to December 2012. Clinical presentation was similar to that reported in other studies. The South African founder mutations that cause HCM were not found in the 42 probands. Ten of 35 index cases (28.6%) tested for mutations in 15 genes had disease-causing mutations in MYH7 (six cases or 60%) and MYBPC3 (four cases or 40%). No disease-causing mutation was found in the other 13 genes screened. The annual mortality rate was 2.9% per annum and overall survival was 74% at 10 years, which was similar to the general South African population. Cox's proportional hazards regression showed that survival was predicted by New York Heart Association (NYHA) functional class at last visit (p equals; 0.026), but not by the presence of a disease-causing mutation (p = 0.474).
  
  
  CONCLUSIONS
  Comprehensive genetic screening was associated with a 29% yield of causal genetic mutations in South African HCM cases, all in MYH7 and MBPC3 genes. A quarter of the patients had died after a decade of follow up, with NYHA functional class serving as a predictor of survival.
authors.affiliation: Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa and The Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa. Email: ntobeko.ntusi@ gmail.com.
authors.forename: Ntobeko A
authors.initials: NA
authors.lastname: Ntusi
authors.affiliation: Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa and The Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, 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 and The Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa; King Saud Bin Abdulaziz University for Medical Sciences, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Motasim
authors.initials: M
authors.lastname: Badri
authors.affiliation: Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Freedom
authors.initials: F
authors.lastname: Gumedze
authors.affiliation: Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa and The Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.
authors.forename: Bongani M
authors.initials: BM
authors.lastname: Mayosi
mesh_terms: D000328:Adult; D000368:Aged; D024722:Cardiac Myosins / Q000235:genetics*; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D005819:Genetic Markers; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human