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.