A novel missense mutation in the myosin binding protein-C gene is responsible for hypertrophic cardiomyopathy with left ventricular dysfunction and dilation in elderly patients

Konno, Tetsuo; Shimizu, Masami; Ino, Hidekazu; Matsuyama, Toru; Yamaguchi, Masato; Terai, Hidenobu; Hayashi, Kenshi; Mabuchi, Tomohito; Kiyama, Masaru; Sakata, Kenji; Hayashi, Tatsumi; Inoue, Masato; Kaneda, Tomoya; Mabuchi, Hiroshi

doi:10.1016/s0735-1097(02)02957-1

Cited by 65 publications

(41 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…24 His LV enddiastolic dimension, end-systolic dimension, and FS values were 56 mm, 48 mm, and 14%, respectively. …”

Section: Genetic Resultsmentioning

confidence: 90%

“…The patient identified in the present study as having a MYBPC3 mutation was the 71-year-old male who had been previously reported 24 and had been diagnosed clinically as having DCM. Genetic analysis revealed that he had an Arg820Gln mutation in MYBPC3, similar to some patients with HCM.…”

Section: Discussionmentioning

confidence: 99%

“…Although it is not clear whether this patient had "burnt-out" HCM or had had DCM from the outset, the findings do suggest that screening for MYBPC3 mutations may be advisable in older Japanese patients with DCM. 24 Ogimoto et al reported a patients with an MYBPC3 mutation who presented with wall thinning and LV dilatation during long-term follow-up. 25 Because matrix disorganization may be associated with progression from HCM to DCM, 26 evaluation of matrix metalloproteinases and their tissue inhibitors as modifying factors, in addition to analysis of disease-causing gene mutations, may provide important information regarding the pathophysiology in patients with DCM.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Gene Mutations in Adult Japanese Patients With Dilated Cardiomyopathy

Shimizu

Ino

Yasuda

et al. 2005

Circ J

Self Cite

View full text Add to dashboard Cite

“…24 His LV enddiastolic dimension, end-systolic dimension, and FS values were 56 mm, 48 mm, and 14%, respectively. …”

Section: Genetic Resultsmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gene Mutations in Adult Japanese Patients With Dilated Cardiomyopathy

Shimizu

Ino

Yasuda

et al. 2005

Circ J

Self Cite

View full text Add to dashboard Cite

“…However, we also included subjects with mutations in MYBPC3 that were reported to be associated with systolic dysfunction. 18,19 Conclusion Non-MYBPC3 mutation carriers developed left ventricular systolic dysfunction more frequently than MYBPC3 mutation carriers, and the majority of sarcomere gene mutation carriers with systolic dysfunction had fatal outcomes during follow-up. This suggests that subjects with mutations in sarcomeric genes require careful management for systolic dysfunction.…”

Section: Discussionmentioning

confidence: 96%

“…11 -13 We have reported that subjects with HCM caused by mutations in TNNT2 and TNNI3 start to develop left ventricular systolic dysfunction at around 40 years of age. 14 -17 In addition, we and others have reported that subjects with HCM caused by mutations in MYBPC3 also progress to left ventricular systolic dysfunction, 18,19 although the clinical features of HCM associated with mutations in MYBPC3 have late onset and a favorable clinical course. 20 These data may provide useful information on genetic counseling strategies of affected subjects with sarcomere gene mutations.…”

Section: Introductionmentioning

confidence: 97%

Impact of Systolic Dysfunction in Genotyped Hypertrophic Cardiomyopathy

Fujino¹,

Konno²,

Hayashi³

et al. 2012

Clinical Cardiology

Self Cite

View full text Add to dashboard Cite

Background: Hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere, and approximately 5% of cases of HCM show systolic dysfunction with poor prognosis. Few data exist regarding the systolic dysfunction in a large population of genotyped HCM subjects. Hypothesis: The aim of this study was to assess the systolic dysfunction and prognosis in sarcomere gene mutation carriers. Methods: The study included 157 sarcomere gene mutation carriers from 69 unrelated HCM families (87 males; mean age, 46.5 ± 20.5 years). After exclusions for systolic dysfunction at baseline, 107 subjects underwent serial echocardiograms. Results: At a mean follow-up of 7.0 years, 12 subjects experienced systolic dysfunction. In multivariate Cox analysis, systolic dysfunction was related to age and ejection fraction at initial evaluation (P < 0.001 and P = 0.020, respectively), and was associated with the absence of mutations in the cardiac myosin-binding protein C gene (MYBPC3) (P = 0.042). When the subjects were divided into MYBPC3 and non-MYBPC3 mutation carriers, and time from birth to development of systolic dysfunction was compared, the rate of systolic dysfunction was higher in the non-MYBPC3 group than in MYBPC3 group (Kaplan-Meier, log-rank test, P = 0.010). After the onset of systolic dysfunction, 11 of 12 subjects died during a mean follow-up of 8.3 years. Conclusions: Non-MYBPC3 mutation carriers developed left ventricular systolic dysfunction more frequently than MYBPC3 mutation carriers, and the majority of sarcomere gene mutation carriers with systolic dysfunction had fatal outcomes during follow-up. This suggests that subjects with mutations in sarcomeric genes require careful management for systolic dysfunction.

show abstract

Homozygosity for a novel splice site mutation in the cardiac myosin‐binding protein C gene causes severe neonatal hypertrophic cardiomyopathy

Xin

Puffenberger

Tumbush

et al. 2007

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy is typically inherited in an autosomal dominant pattern and has a variable age of onset and prognosis. Mutations in the myosin-binding protein C (MYBPC3) gene are one of the most frequent genetic causes of the disease. Patients with MYBPC3 mutations generally have a late onset and a relatively good prognosis. We report here more than 20 Old Order Amish children with severe neonatal hypertrophic cardiomyopathy caused by a novel homozygous splice site mutation in the MYBPC3 gene. The affected children typically presented with signs and symptoms of congestive heart failure during the first 3 weeks of life. Echocardiography revealed hypertrophic non-obstructive cardiomyopathy. These children had a life span averaging 3-4 months. All patients died from heart failure before 1 year of age unless they received a heart transplant. A genome-wide mapping study was performed in three patients. The disease related gene was localized to a 4.6 Mb region on chromosome 11p11.2-p11.12. This homozygous block contained MYBPC3, a previously identified cardiomyopathy related gene. We identified a novel homozygous mutation, c.3330 + 2T> G, in the splice-donor site of MYBPC3 intron 30. The mutation resulted in skipping of the 140-bp exon 30, which led to a frame shift and premature stop codon in exon 31 (p.Asp1064GlyfsX38). We have found a substantial incidence of this phenotype in Old Order Amish communities. It is also concerning that many unidentified heterozygous individuals who are at risk for development of hypertrophic cardiomyopathy do not receive proper medical attention in the communities.

show abstract

A novel missense mutation in the myosin binding protein-C gene is responsible for hypertrophic cardiomyopathy with left ventricular dysfunction and dilation in elderly patients

Cited by 65 publications

References 28 publications

Gene Mutations in Adult Japanese Patients With Dilated Cardiomyopathy

Gene Mutations in Adult Japanese Patients With Dilated Cardiomyopathy

Impact of Systolic Dysfunction in Genotyped Hypertrophic Cardiomyopathy

Homozygosity for a novel splice site mutation in the cardiac myosin‐binding protein C gene causes severe neonatal hypertrophic cardiomyopathy

Contact Info

Product

Resources

About