Prevalence and Distribution of Sarcomeric Gene Mutations in Japanese Patients With Familial Hypertrophic Cardiomyopathy

Otsuka, Haruna; Arimura, Takuro; Abe, Tadaaki; Kawai, Hiroya; Aizawa, Yoshifusa; Kubo, Toru; Kitaoka, Hiroaki; Nakamura, Hiroshi; Nakamura, Kazufumi; Okamoto, Hiroshi; Ichida, Fukiko; Ayusawa, Mamoru; Nunoda, Shinichi; Isobe, Mitsuaki; Matsuzaki, Masunori; Doi, Yasufumi; Fukuda, Keiichi; Sasaoka, Taishi; Izumi, Toru; Ashizawa, Naoto; Kimura, Akinori

doi:10.1253/circj.cj-11-0876

Cited by 83 publications

(49 citation statements)

References 32 publications

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“…In these adult cases, a more severe HCM phenotype is generally seen, characterized by an earlier age of onset around the second decade or during childhood (Table 2). 6,14,15,[20][21][22][23][24][25][26][27][28][29][30] In a recent study on sarcomeric protein gene variants in childhood-onset HCM, 6 out of 84 children (7%) had compound variants. 6 This suggests that a gene-dosage effect might be responsible for manifestations at a younger age.…”

Section: Discussionmentioning

confidence: 99%

Compound heterozygous or homozygous truncating MYBPC3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects

et al. 2014

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Familial hypertrophic cardiomyopathy (HCM) is usually caused by autosomal dominant pathogenic mutations in genes encoding sarcomeric or sarcomere-associated cardiac muscle proteins. The disease mainly affects adults, although young children with severe HCM have also been reported. We describe four unrelated neonates with lethal cardiomyopathy, and performed molecular studies to identify the genetic defect. We also present a literature overview of reported patients with compound heterozygous or homozygous pathogenic MYBPC3 mutations and describe their clinical characteristics. All four children presented with feeding difficulties, failure to thrive, and dyspnea. They died from cardiac failure before age 13 weeks. Features of left ventricular noncompaction were diagnosed in three patients. In the fourth, hypertrabeculation was not a clear feature, but could not be excluded. All of them had septal defects. Two patients were compound heterozygotes for the pathogenic c.2373dup p. (Trp792fs) and c.2827C4T p.(Arg943*) mutations, and two were homozygous for the c.2373dup and c.2827C4T mutations. All patients with biallelic truncating pathogenic mutations in MYBPC3 reported so far (n = 21) were diagnosed with severe cardiomyopathy and/or died within the first few months of life. In 62% (13/21), septal defects or a patent ductus arteriosus accompanied cardiomyopathy. In contrast to heterozygous pathogenic mutations, homozygous or compound heterozygous truncating pathogenic MYBPC3 mutations cause severe neonatal cardiomyopathy with features of left ventricular noncompaction and septal defects in approximately 60% of patients.

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Section: Discussionmentioning

confidence: 99%

Compound heterozygous or homozygous truncating MYBPC3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects

et al. 2014

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“…9 They found that specific mutation of Glu163Lys in the TNNT2 gene was found only in the Kyushu area, Ser593fs/8 in the MYBPC3 gene was found mainly in the Shikoku area, and Arg92Trp in the TNNT2 gene was mainly observed in the Kyushu and Kansai areas. These findings indicate the specificity of gene mutations in specific ethnic groups.…”

Section: Geographic Distribution Of Hcm-associated Gene Mutationsmentioning

confidence: 98%

Multicenter Study of the Prevalence and Distribution of Sarcometric Gene Mutations in Familial Hypertrophic Cardiomyopathy

Niwano

2012

Circ J

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“…At present there have been over 1,000 different types of gene mutations reported. In Japan the comprehensive sequencing of the sarcomere protein gene excluding titin has been analyzed in patients with HCM, revealing a high incidence of MTBPC3, MTH7 and TNNT2 [3]. It has been reported that some sarcomere protein gene mutations correlate with severe hypertrophy, localization, age at onset, clinical symptoms and clinical progress.…”

Section: Outline Of Genetic Analysis Of Hypertrophic Cardiomyopathymentioning

confidence: 99%

Clinical Implication of Genetic Testing for Hypertrophic Cardiomyopathy

Komamura¹

2013

Human Genet Embryol

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Hypertrophic cardiomyopathy (HCM) is caused by a dominant mutation of the sarcomere protein gene in approximately 60% of cases. Genetic testing of HCM has several benefits. Diagnosis can be confirmed if the sarcomere protein gene mutation is identified. Genetic testing enables to follow-up blood relatives who are mutationpositive only, and can identify asymptomatic and non-onset patients. Relatives with negative results of genetic testing could be freed from anguish. On the other hand, genetic testing has some disadvantages. Treatment often does not change after testing. Forty percent of cases has unknown causative genes. Relationship between gene mutation and clinical findings or treatment responsiveness is little known, and so on.Many issues need to be resolved to incorporate genetic diagnosis into daily practice for HCM. However, genetic testing for HCM cannot be regarded as unnecessary and expensive debauchery, but rather represents a valuable measure in the medical facilities. Although there still remain questions about genetic diagnosis of HCM, accumulated knowledge to date is fairly enough to establish the genetic testing as a useful tool for individualized management of HCM patients and their families.

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Prevalence and Distribution of Sarcomeric Gene Mutations in Japanese Patients With Familial Hypertrophic Cardiomyopathy

Cited by 83 publications

References 32 publications

Compound heterozygous or homozygous truncating MYBPC3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects

Compound heterozygous or homozygous truncating MYBPC3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects

Multicenter Study of the Prevalence and Distribution of Sarcometric Gene Mutations in Familial Hypertrophic Cardiomyopathy

Clinical Implication of Genetic Testing for Hypertrophic Cardiomyopathy

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