TY - JOUR
T1 - Clinical features, survival experience, and profile of plakophylin-2 gene mutations in participants of the Arrhythmogenic Right Ventricular Cardiomyopathy Registry of South Africa
AU - Watkins, David A.
AU - Hendricks, Neil
AU - Shaboodien, Gasnat
AU - Mbele, Mzwandile
AU - Parker, Michelle
AU - Vezi, Brian Z.
AU - Latib, Azeem
AU - Chin, Ashley
AU - Little, Francesca
AU - Badri, Motasim
AU - Moolman-Smook, Johanna C.
AU - Okreglicki, Andrzej
AU - Mayosi, Bongani M.
N1 - Funding Information:
This work is supported by grants from the International Centre for Genetic Engineering and Biotechnology (ICGEB), National Research Foundation (NRF), Medical Research Council of South Africa (MRC), Cardiac Arrhythmia Society of Southern Africa (CASSA), and Lily and Ernst Hausmann Research Trust. The authors of this manuscript have no conflict of interest.
PY - 2009/11
Y1 - 2009/11
N2 - Little is known about arrhythmogenic right ventricular cardiomyopathy (ARVC) in Africa. The objective of this study was to delineate the clinical characteristics, survival, and genetics of ARVC in South Africa. Information on clinical presentation, electrocardiographic and cardiac imaging findings, histology, and outcome of cases with suspected ARVC was collected using the standardised form of the ARVC Registry of South Africa. Genomic DNA was screened for mutations in plakophylin-2 (PKP2) gene. Survival and its predictors were analyzed using the Kaplan-Meier and Cox proportional hazards regression methods, respectively. Fifty unrelated cases who met the diagnostic criteria for ARVC were enrolled between January 2004 and April 2009. Clinical presentation was similar to that reported in other studies. Annual mortality rate was 2.82%, five-year cumulative mortality rate 10%, and mean age at death 36.9 ± 14.7 years. Overall survival was similar to the general South African population (P = 0.25). Independent risk factors for death were syncope (Hazard Ratio [HR] 10.73, 95% Confidence Interval [CI] 1.88-61.18, P = 0.008) and sustained ventricular tachycardia (HR = 22.97, 95%CI 2.33-226.18, P = 0.007). Seven PKP2 gene mutations were found in 9/36 (25%) unrelated participants, five being novel. The novel C1162T mutation occurred in four white South Africans sharing a common haplotype, suggesting a founder effect. Compound heterozygotes exhibited a severe phenotype signifying an allele dose effect. ARVC is associated with early mortality that is no different to the general South Africa population whose lifespan is shortened by HIV/AIDS. PKP2 gene mutations are common, have an allele dose effect, and a novel founder effect in white South Africans.
AB - Little is known about arrhythmogenic right ventricular cardiomyopathy (ARVC) in Africa. The objective of this study was to delineate the clinical characteristics, survival, and genetics of ARVC in South Africa. Information on clinical presentation, electrocardiographic and cardiac imaging findings, histology, and outcome of cases with suspected ARVC was collected using the standardised form of the ARVC Registry of South Africa. Genomic DNA was screened for mutations in plakophylin-2 (PKP2) gene. Survival and its predictors were analyzed using the Kaplan-Meier and Cox proportional hazards regression methods, respectively. Fifty unrelated cases who met the diagnostic criteria for ARVC were enrolled between January 2004 and April 2009. Clinical presentation was similar to that reported in other studies. Annual mortality rate was 2.82%, five-year cumulative mortality rate 10%, and mean age at death 36.9 ± 14.7 years. Overall survival was similar to the general South African population (P = 0.25). Independent risk factors for death were syncope (Hazard Ratio [HR] 10.73, 95% Confidence Interval [CI] 1.88-61.18, P = 0.008) and sustained ventricular tachycardia (HR = 22.97, 95%CI 2.33-226.18, P = 0.007). Seven PKP2 gene mutations were found in 9/36 (25%) unrelated participants, five being novel. The novel C1162T mutation occurred in four white South Africans sharing a common haplotype, suggesting a founder effect. Compound heterozygotes exhibited a severe phenotype signifying an allele dose effect. ARVC is associated with early mortality that is no different to the general South Africa population whose lifespan is shortened by HIV/AIDS. PKP2 gene mutations are common, have an allele dose effect, and a novel founder effect in white South Africans.
KW - Arrhythmogenic right ventricular cardiomyopathy
KW - Registry
KW - South Africa
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=75549084678&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75549084678&partnerID=8YFLogxK
U2 - 10.1016/j.hrthm.2009.08.018
DO - 10.1016/j.hrthm.2009.08.018
M3 - Article
C2 - 19880068
AN - SCOPUS:75549084678
SN - 1547-5271
VL - 6
SP - S10-S17
JO - Heart Rhythm
JF - Heart Rhythm
IS - 11 SUPPL.
ER -