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

被引：28

作者：

Jaaskelainen, Pertti ^{[1
]}

Helio, Tiina ^{[2
]}

Aalto-Setala, Katriina ^{[3
]}

Kaartinen, Maija ^{[2
]}

Ilveskoski, Erkki ^{[3
]}

Hamalainen, Liisa ^{[4
]}

Melin, John ^{[5
]}

Nieminen, Markku S. ^{[2
]}

Laakso, Markku ^{[6
]}

Kuusisto, Johanna ^{[6
]}

Kervinen, Helena ^{[7
]}

Mustonen, Juha ^{[8
]}

Juvonen, Jukka ^{[9
]}

Niemi, Mari ^{[10
]}

Uusimaa, Paavo ^{[11
]}

Huttunen, Matti ^{[12
]}

Kotila, Matti ^{[13
]}

Pietila, Mikko ^{[14
]}

机构：

[1] Kuopio Univ Hosp, Ctr Heart, FIN-70211 Kuopio, Finland

[2] Univ Helsinki, Cent Hosp, Helsinki, Finland

[3] Tampere Univ Hosp, Heart Ctr Co, Tampere, Finland

[4] Vaasa Cent Hosp, Vaasa, Finland

[5] Cent Finland Cent Hosp, Jyvaskyla, Finland

[6] Univ Eastern Finland, Ctr Med & Clin Res, Dept Med, FIN-70211 Kuopio, Finland

[7] Hyvinkaa Hosp, Hyvinkaa, Finland

[8] N Karelia Cent Hosp, Joensuu, Finland

[9] Kainuu Cent Hosp, Kajaani, Finland

[10] Kokkola Cent Hosp, Kokkola, Finland

[11] Oulu Univ Hosp, Oulu, Finland

[12] Savonlinna Cent Hosp, Savonlinna, Finland

[13] Seinajoki Cent Hosp, Seinajoki, Finland

[14] Turku Univ Hosp, FIN-20520 Turku, Finland

来源：

ANNALS OF MEDICINE | 2013年 / 45卷 / 01期

基金：

芬兰科学院;

关键词：

Alpha-tropomyosin; Finnish population; founder mutation; hypertrophic cardiomyopathy; myosin-binding protein C; GENOTYPE CLINICALLY USEFUL; PREDICTING-PROGNOSIS; HEAVY-CHAIN; SPECTRUM; DISEASE; PREVALENCE; GENETICS;

D O I：

10.3109/07853890.2012.671534

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background. Hypertrophic cardiomyopathy (HCM) is predominantly caused by a large number of various mutations in the genes encoding sarcomeric proteins. However, two prevalent founder mutations for HCM in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes have previously been identified in eastern Finland. Objective. To assess the prevalence of these founder mutations in a large population of patients with HCM from all over Finland. Patients and methods. We screened for two founder mutations (TPM1-D175N and MYBPC3-Q1061X) in 306 unrelated Finnish patients with HCM from the regions covering a population of similar to 4,000,000. Results. The TPM1-D175N mutation was found in 20 patients (6.5%) and the MYBPC3-Q1061X in 35 patients (11.4%). Altogether, the two mutations accounted for 17.9% of the HCM cases. In addition, 61 and 59 relatives of the probands were found to be carriers of TPM1-D175N and MYBPC3-Q1061X, respectively. The mutations showed regional clustering. TPM1-D175N was prevalent in central and western Finland, and MYBPC3-Q1061X in central and eastern Finland. Conclusion. The TPM1-D175N and MYBPC3-Q1061X mutations account for a substantial part of all HCM cases in the Finnish population, indicating that routine genetic screening of these mutations is warranted in Finnish patients with HCM.

引用

页码：85 / 90

页数：6

共 26 条

[1] The 2373insG mutation in the MYBPC3 gene is a founder mutation, which accounts for nearly one-fourth of the HCM cases in the Netherlands
Alders, M
Jongbloed, R
Deelen, W
van den Wijngaard, A
Doevendans, P
Ten Cate, F
Regitz-Zagrosek, V
Vosberg, HP
van Langen, I
Wilde, A
Dooijes, D
Mannens, M
[J]. EUROPEAN HEART JOURNAL, 2003, 24 (20) : 1848 - 1853
[2] Diagnostic Yield, Interpretation, and Clinical Utility of Mutation Screening of Sarcomere Encoding Genes in Danish Hypertrophic Cardiomyopathy Patients and Relatives
Andersen, Paal Skytt
Havndrup, Ole
Hougs, Lotte
Sorensen, Karina M.
Jensen, Morten
Larsen, Lars Allan
Hedley, Paula
Thomsen, Alex Rojas Bie
Moolman-Smook, Johanna
Christiansen, Michael
Bundgaard, Henning
[J]. HUMAN MUTATION, 2009, 30 (03) : 363 - 370
[3] Bottinelli R, 1998, CIRC RES, V82, P106
[4] Founder mutations in hypertrophic cardiomyopathy patients in the Netherlands
Christiaans, I.
Nannenberg, E. A.
Dooijes, D.
Jongbloed, R. J. E.
Michels, M.
Postema, P. G.
Majoor-Krakauer, D.
van den Wijngaard, A.
Mannens, M. M. A. M.
van Tintelen, J. P.
van Langen, I. M.
Wilde, A. A. M.
[J]. NETHERLANDS HEART JOURNAL, 2010, 18 (05) : 248 - 254
[5] Clinical features of hypertrophic cardiomyopathy caused by mutation of a ''hot spot'' in the alpha-tropomyosin gene
Coviello, DA
Maron, BJ
Spirito, P
Watkins, H
Vosberg, HP
Thierfelder, L
Schoen, FJ
Seidman, JG
Seidman, CE
[J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1997, 29 (03) : 635 - 640
[6] Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy
Erdmann, J
Daehmlow, S
Wischke, S
Senyuva, M
Werner, U
Raible, J
Tanis, N
Dyachenko, S
Hummel, M
Hetzer, R
Regitz-, V
[J]. CLINICAL GENETICS, 2003, 64 (04) : 339 - 349
[7] A molecular screening strategy based on β-myosin heavy chain, cardiac myosin binding protein C and troponin T genes in Italian patients with hypertrophic cardiomyopathy
Girolami, Francesca
Olivotto, Iacopo
Passerini, Ilaria
Zachara, Elisabetta
Nistri, Stefano
Re, Federica
Fantini, Silvia
Baldini, Katia
Torricelli, Francesca
Cecchi, Franco
[J]. JOURNAL OF CARDIOVASCULAR MEDICINE, 2006, 7 (08) : 601 - 607
[8] Is genotype clinically useful in predicting prognosis in hypertrophic cardiomyopathy? Genetics and Clinical Destiny: Improving Care in Hypertrophic Cardiomyopathy
Ho, Carolyn Y.
[J]. CIRCULATION, 2010, 122 (23) : 2430 - 2440
[9] The cardiac β-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population
Jääskeläinen, P
Soranta, M
Miettinen, R
Saarinen, L
Pihlajamäki, J
Silvennoinen, K
Tikanoja, T
Laakso, M
Kuusisto, J
[J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1998, 32 (06) : 1709 - 1716
[10] Genetics of hypertrophic cardiomyopathy in eastern Finland:: few founder mutations with benign or intermediary phenotypes
Jääskeläinen, P
Miettinen, R
Kärkkäinen, P
Toivonen, L
Laakso, M
Kuusisto, J
[J]. ANNALS OF MEDICINE, 2004, 36 (01) : 23 - 32

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