Significance of Sarcomere Gene Mutations Analysis in the End-Stage Phase of Hypertrophic Cardiomyopathy

被引：78

作者：

Biagini, Elena ^{[1
]}

Olivotto, Iacopo ^{[2
]}

Iascone, Maria ^{[4
]}

Parodi, Maria I. ^{[5
]}

Girolami, Francesca ^{[3
]}

Frisso, Giulia ^{[7
,8
]}

Autore, Camillo ^{[9
]}

Limongelli, Giuseppe ^{[10
]}

Cecconi, Massimiliano ^{[5
]}

Maron, Barry J. ^{[11
]}

Maron, Martin S. ^{[12
]}

Rosmini, Stefania

Formisano, Francesco ^{[6
]}

Musumeci, Beatrice ^{[9
]}

Cecchi, Franco ^{[2
]}

Iacovoni, Attilio ^{[13
]}

Haas, Tammy S. ^{[11
]}

Reggiani, Maria L. Bacchi ^{[1
]}

Ferrazzi, Paolo ^{[14
]}

Salvatore, Francesco ^{[7
,8
]}

Spirito, Paolo ^{[6
]}

Rapezzi, Claudio ^{[1
]}

机构：

[1] Univ Bologna, Dipartimento Med Specialist Diagnost & Sperimenta, Alma Mater Studiorum, I-40126 Bologna, Italy

[2] Azienda Osped Univ Careggi, Ctr Riferimento Cardiomiopatie, Florence, Italy

[3] Azienda Osped Univ Careggi, SOD Diagnost Genet, Florence, Italy

[4] Osped Riuniti Bergamo, USSD Lab Genet Med, I-24100 Bergamo, Italy

[5] EO Osped Galliera, SC Lab Genet Umana, Genoa, Italy

[6] EO Osped Galliera, SC Cardiol, Genoa, Italy

[7] Univ Naples Federico II, IRCCS Fdn SDN, CEINGE Biotecnol Avanzate Scarl Napoli, Naples, Italy

[8] Univ Naples Federico II, IRCCS Fdn SDN, Dipartimento Med Mol & Biotecnol Med, Naples, Italy

[9] Univ Roma La Sapienza, Dipartimento Med Clin & Mol, Div Cardiol, I-00185 Rome, Italy

[10] Univ Naples 2, Dipartimento Cardiol, Naples, Italy

[11] Minneapolis Heart Inst Fdn, Hypertroph Cardiomyopathy Ctr, Minneapolis, MN USA

[12] Hypertroph Cardiomyopathy Ctr, Tufts Med Ctr, Boston, MA USA

[13] Osped Riuniti Bergamo, Dipartimento Cardiovasc, I-24100 Bergamo, Italy

[14] Policlin Monza, Monza, Italy

来源：

AMERICAN JOURNAL OF CARDIOLOGY | 2014年 / 114卷 / 05期

关键词：

CLINICAL-SIGNIFICANCE; SYSTOLIC DYSFUNCTION; MYOCARDIAL FIBROSIS; SUDDEN-DEATH; RISK-FACTORS; PREVALENCE; COMPOUND; IMPAIRMENT; DIAGNOSIS; SPECTRUM;

D O I：

10.1016/j.amjcard.2014.05.065

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

End-stage hypertrophic cardiomyopathy (ES-HC) has an ominous prognosis. Whether genotype can influence ES-HC occurrence is unresolved. We assessed the spectrum and clinical correlates of HC-associated mutations in a large multicenter cohort with end-stage ES-HC. Sequencing analysis of 8 sarcomere genes (MYH7, MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC1) and 2 metabolic genes (PRKAG2 and LAMP2) was performed in 156 ES-HC patients with left ventricular (LV) ejection fraction (EF) <50%. A comparison among mutated and negative ES-HC patients and a reference cohort of 181 HC patients with preserved LVEF was performed. Overall, 131 mutations (36 novel) were identified in 104 ES-HC patients (67%) predominantly affecting MYH7 and MYBPC3 (80%). Complex genotypes with double or triple mutations were present in 13% compared with 5% of the reference cohort (p = 0.013). The distribution of mutations was otherwise indistinguishable in the 2 groups. Among ES-HC patients, those presenting at first evaluation before the age of 20 had a 30% prevalence of complex genotypes compared with 19% and 21% in the subgroups aged 20 to 59 and >= 60 years (p = 0.003). MYBPC3 mutation carriers with ES-HC were older than patients with MYH7, other single mutations, or multiple mutations (median 41 vs 16; 26, and 28 years, p <= 0.001). Outcome of ES-HC patients was severe irrespective of genotype. In conclusion, the ES phase of HC is associated with a variable genetic substrate, not distinguishable from that of patients with HC and preserved EF, except for a higher frequency of complex genotypes with double or triple mutations of sarcomere genes. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：769 / 776

页数：8