Details

Autor(en) / Beteiligte

• Biagini, Elena, MD, PhD
• Olivotto, Iacopo, MD
• Iascone, Maria, BSc, PhD
• Parodi, Maria I., BSc
• Girolami, Francesca, BSc
• Frisso, Giulia, MD, PhD
• Autore, Camillo, MD
• Limongelli, Giuseppe, MD
• Cecconi, Massimiliano, BSc
• Maron, Barry J., MD
• Maron, Martin S., MD
• Rosmini, Stefania, MD
• Formisano, Francesco, MD
• Musumeci, Beatrice, MD
• Cecchi, Franco, MD
• Iacovoni, Attilio, MD
• Haas, Tammy S., RN
• Bacchi Reggiani, Maria L., MSc, MStat
• Ferrazzi, Paolo, MD
• Salvatore, Francesco, MD, PhD
• Spirito, Paolo, MD
• Rapezzi, Claudio, MD

Titel

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

Ist Teil von

• The American journal of cardiology, 2014-09, Vol.114 (5), p.769-776

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.