Sequence analysis of myozenin 2 in 438 European patients with familial hypertrophic cardiomyopathy.
BACKGROUND
Familial hypertrophic cardiomyopathy (HCM) is an allelic cardiac disorder characterized by increased ventricular wall mass and sudden cardiac death. A variety of dominant single-gene mutations in sarcomeric genes have been identified, indicating a highly heterogeneous genetic etiology. MYOZ2 encodes for sarcomeric calsarcin-1 located in the myocardial z-disc, a focal point of HCM disease genes. Very recently mutations in MYOZ2 were reported as a cause for HCM. To assess the prevalence of MYOZ2 mutations among European HCM patients, coding exons weree analyzed for genetic variants in 438 patients.


METHODS
Four hundred thirty-eight patients with HCM in four European cardiovascular centers were recruited. The coding region of MYOZ2 was directly sequenced in all the HCM subjects.


RESULTS
Two non-synonymous polymorphisms in exon 2 (rs17851524) and exon 5 (rs7687613) of MYOZ2 were identified in eight and twenty-two patients, respectively. However, no disease-causing mutations could be identified in this large cohort of HCM patients.


CONCLUSIONS
Although a large cohort of more than 400 patients with familial HCM was screened, a disease-associated mutation in MYOZ2 was not identified. When these results are combined with previous reports, it can be concluded that MYOZ2 mutations are rare causes of familial HCM.
Posch
Maximilian G
MG
Department of Cardiology Charite, Universitatsmedizin Berlin, Campus Virchow, Berlin, Germany.
Thiemann
Laura
L
Tomasov
Pavol
P
Veselka
Josef
J
Cardim
Nuno
N
Garcia-Castro
Monica
M
Coto
Eliecer
E
Perrot
Andreas
A
Geier
Christian
C
Dietz
Rainer
R
Haverkamp
Wilhelm
W
Ozcelik
Cemil
C
D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*
D002352:Carrier Proteins; C419779:MYOZ2 protein, human; D009124:Muscle Proteins