Two founder mutations in the alpha-tropomyosin and the cardiac myosin-binding protein C genes are common causes of hypertrophic cardiomyopathy in the Finnish population

Figures & data

Table I. Clinical characteristics of the index patients with hypertrophic cardiomyopathy.

	All (n = 306)	TPM1-D175N (n = 20)	MYBPC3-Q1061X (n = 35)
Men/women	185/121 (60/40%)	9/11 (45/55%)	23/12 (66/34%)
Age (years)	53 ± 15 (16–85)	52 ± 15 (18–77)	49 ± 12 (21–76)
Family history
HCM	83 (27%)	15 (75%)	12 (34%)
Sudden cardiac death	102 (33%)	11 (55%)	9 (26%)
Cardiac symptoms
Dyspnea	131 (43%)	10 (50%)	11 (31%)
Chest pain	43 (14%)	4 (25%)	4 (11%)
Syncope/presyncope	84 (27%)	9 (45%)	9 (26%)
NYHA class
1–2	260 (85%)	19 (95%)	31 (89%)
3–4	22 (7%)	1 (5%)	1 (3%)
History of arrhythmias
Paroxysmal atrial fibrillation	56 (18%)	4 (20%)	5 (14%)
Chronic atrial fibrillation	21 (7%)	4 (20%)	3 (9%)
Sustained ventricular tachycardia	10 (3%)	0 (0%)	2 (6%)
Ventricular fibrillation	14 (5%)	2 (10%)	1 (3%)
History of systolic congestive heart failure	12 (4%)	1 (5%)	0 (0%)
History of ICD implantation	30 (10%)	2 (10%)	7 (20%)
History of myectomy	7 (2%)	2 (10%)	0 (0%)
Echocardiography
Maximal thickness of LV (mm)	20 ± 4 (10–38)	20 ± 2 (15–24)	22 ± 5 (15–38)
LVEDD (mm)	46 ± 7	43 ± 6	45 ± 6
LVESD (mm)	29 ± 7	27 ± 6	27 ± 6
Ejection fraction (%)	68 ± 11	67 ± 11	70 ± 9
Maximal flow velocity at LVOT (m/s)	1.8 ± 1.9	1.3 ± 0.6	1.5 ± 0.7
Bicycle ergometry (n = 214)
Maximum load (W)	163 ± 69	120 ± 57	166 ± 65
Abnormal systolic BP response	21 (10%)	4 (20%)	1 (3%)
Holter ECG registration (n = 249)
Non-sustained ventricular tachycardia	50 (20%)	2 (10%)	8 (23%)
Atrial fibrillation	39 (16%)	4 (20%)	3 (9%)

Data are n (%) or mean ± SD.

BP = blood pressure; HCM = hypertrophic cardiomyopathy; ICD = implantable cardioverter defibrillator; LV = left ventricle; LVEDD = left ventricular end-diastolic dimension; LVESD = left ventricular end-systolic dimension; LVOT = left ventricular outflow tract; MYBPC3 = cardiac myosin-binding protein C gene; TPM1 = alpha-tropomyosin gene.

Table II. Frequencies of the mutations TPM1-D175N and MYBPC3-Q1061X according to study center.

Center	No. of patients	TPM1-D175N	%	MYBPC3-Q1061X	%
1 Helsinki	122	4	3.3	11	9.0
2 Tampere	54	7	13.0	4	7.4
3 Kuopio	33	0	0	8	24.2
4 Jyväskylä	30	2	6.7	8	26.7
5 Seinäjoki	17	3	17.6	1	5.9
6 Joensuu	16	0	0	0	0
7 Kajaani	10	0	0	1	10
8 Kokkola	7	0	0	0	0
9 Oulu	6	1	16.7	1	16.7
10 Turku	6	0	0	1	16.7
11 Vaasa	4	2	50	0	0
12 Savonlinna	1	1	100	0	0
Total	306	20		35

MYBPC3 = cardiac myosin-binding protein C gene; TPM1 = alpha-tropomyosin gene.

Figure 1. Prevalence of the mutations TPM1 (alpha-tropomyosin)-D175N and MYBPC3 (cardiac myosin-binding protein C)-Q1061X in the five largest study centers (Helsinki, Tampere, Kuopio, Jyväskylä, and Seinäjoki). Hospital districts are numbered (1–12) corresponding to the numbers in Table II.