Familial Hypertrophic Cardiomyopathy Unexplained left ventricular hypertrophy (LVH) occurs in approximately one in 500 individuals, with approximately 55%-70% attributable to familial hypertrophic cardiomyopathy (HCM). At least thirteen different genes are known to be associated with HCM, each of which encode different components of the sarcomere. DNA testing is based on sequence analysis of the coding regions of five genes: MYBPC3, MYH7, TNNT2, TNNI3 and TPM1. This analysis detects >99% of point mutations and small deletions and insertions that may occur in these genes. To detect large genomic deletions and duplications, multiplex ligation-dependent probe amplification (MLPA) using the two available kits for analysis of MYBPC3 and TNNT2 is also performed. Since mutations of the five genes tested account for approximately 92% of HCM cases, a negative result does not rule out a diagnosis of familial hypertrophic cardiomyopathy. Test available: Sample requirements: Estimated turn around time: Routine, Prenatal* 10 mL blood in EDTA tube** 3 mL blood in EDTA tube (infant only –under 1 year of age)** Routine – 4-6 weeks * Inquiries about prenatal testing should be directed to the Laboratory. ** Samples are accepted through Cardiology and Genetics Clinics only. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Hereditary arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heterogenous disease characterized by progressive fibrofatty replacement of myocardium tissue that predisposes individuals to ventricular tachycardia. It is most frequently inherited as an autosomal dominant trait, although autosomal recessive inheritance patterns have also been described. At least twelve different loci have been linked to ARVC. Most clinically confirmed cases are attributed to mutations in either the PKP2, DSG2, or DSP genes (11-43%, 12-40% and 6-16% of cases, respectively). Of relevance to the Canadian population, a single mutation of the TMEM3 gene, c.1073C>T, has also been described in unrelated families from an isolated region in Newfoundland. DNA testing for ARVC is based on sequence analysis of the coding regions of the PKP2, DSG2 and DSP genes and the c.1073C>T mutation in the TMEM3 gene. Large genomic deletions and duplications of the PKP2 and DSP genes are further assessed by muliplex ligation-dependent probe amplification (MLPA) using an available kit. Mutations in the genes not being tested account for only a small proportion of cases described to date. Given the heterogeneity of ARVC, a negative test result does not rule out a diagnosis of arrhythmogenic right ventricular cardiomyopathy. Test available: Sample requirements: Estimated Turn around time: Routine, Prenatal* 10 mL blood in EDTA tube ** 3 mL blood in EDTA tube (infant only –under 1 year of age) ** Routine – 4-6 weeks Newborn – 7 working days * Inquiries about prenatal testing should be directed to the Laboratory. ** Samples are accepted through Cardiology and Genetics Clinics only.