PMID- 27841901
OWN - NLM
STAT- MEDLINE
DCOM- 20170227
LR  - 20181113
IS  - 1680-0745 (Electronic)
IS  - 1995-1892 (Print)
IS  - 1015-9657 (Linking)
VI  - 27
IP  - 3
DP  - 2016 May/Jun
TI  - Clinical features, spectrum of causal genetic mutations and outcome of 
      hypertrophic cardiomyopathy in South Africans.
PG  - 152-158
LID - 10.5830/CVJA-2015-075 [doi]
AB  - 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 beta-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), alpha-actin 
      (ACTC1), cysteine and glycine-rich protein 3 (CSRP3), AMP-activated protein 
      kinase (PRKAG2), alpha-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.
FAU - Ntusi, Ntobeko A
AU  - Ntusi NA
AD  - 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.
FAU - Shaboodien, Gasnat
AU  - Shaboodien G
AD  - 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.
FAU - Badri, Motasim
AU  - Badri M
AD  - 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.
FAU - Gumedze, Freedom
AU  - Gumedze F
AD  - Department of Statistical Sciences, University of Cape Town, Cape Town, South 
      Africa.
FAU - Mayosi, Bongani M
AU  - Mayosi BM
AD  - 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.
LA  - eng
PT  - Journal Article
PL  - South Africa
TA  - Cardiovasc J Afr
JT  - Cardiovascular journal of Africa
JID - 101313864
RN  - 0 (Carrier Proteins)
RN  - 0 (Genetic Markers)
RN  - 0 (MYH7 protein, human)
RN  - 0 (myosin-binding protein C)
RN  - EC 3.6.1.- (Cardiac Myosins)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cardiac Myosins/*genetics
MH  - Cardiomyopathy, Hypertrophic, 
      Familial/diagnosis/*genetics/mortality/physiopathology
MH  - Carrier Proteins/*genetics
MH  - DNA Mutational Analysis
MH  - Echocardiography
MH  - Electrocardiography
MH  - Female
MH  - Genetic Markers
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Myosin Heavy Chains/*genetics
MH  - Phenotype
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Prospective Studies
MH  - Risk Factors
MH  - South Africa/epidemiology
MH  - Time Factors
PMC - PMC5101433
EDAT- 2016/11/15 06:00
MHDA- 2017/02/28 06:00
PMCR- 2016/05/01
CRDT- 2016/11/15 06:00
PHST- 2014/05/02 00:00 [received]
PHST- 2015/09/15 00:00 [accepted]
PHST- 2016/11/15 06:00 [entrez]
PHST- 2016/11/15 06:00 [pubmed]
PHST- 2017/02/28 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - 10.5830/CVJA-2015-075 [doi]
PST - ppublish
SO  - Cardiovasc J Afr. 2016 May/Jun;27(3):152-158. doi: 10.5830/CVJA-2015-075.