Compound and Digenic Heterozygosity in Desmosome Genes as a Cause of Arrhythmogenic Right Ventricular Cardiomyopathy in Japanese Patients

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著者

    • NAKAJIMA Tadashi
    • Department of Medicine and Biological Science, Gunma University Graduate School of Medicine
    • KANEKO Yoshiaki
    • Department of Medicine and Biological Science, Gunma University Graduate School of Medicine
    • IRIE Tadanobu
    • Department of Medicine and Biological Science, Gunma University Graduate School of Medicine
    • TAKAHASHI Rieko
    • Department of Medicine and Biological Science, Gunma University Graduate School of Medicine
    • KATO Toshimitsu
    • Department of Medicine and Biological Science, Gunma University Graduate School of Medicine
    • IIJIMA Takafumi
    • Department of Medicine and Biological Science, Gunma University Graduate School of Medicine
    • ISO Tatsuya
    • Department of Medicine and Biological Science, Gunma University Graduate School of Medicine
    • KURABAYASHI Masahiko
    • Department of Medicine and Biological Science, Gunma University Graduate School of Medicine

抄録

<b><i>Background:</i></b> Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary disorder mostly caused by desmosome gene mutations. Recent comprehensive desmosome mutation analyses of Caucasian ARVC patients have revealed the presence of not only a single heterozygous mutation, but also compound and digenic heterozygosity. However, the genetic basis of Japanese ARVC remains poorly elucidated. <b><i>Methods and Results:</i></b> The subjects were 7 definite and 1 possible ARVC probands (6 males, 16-76 years of age), and their family members. Genetic screening for major ARVC-causing genes (junction plakoglobin, desmoplakin, plakophilin-2 (PKP2), desmoglein-2 (DSG2), and desmocollin-2) was performed. We identified 3 cases of compound heterozygosities (Case 1: DSG2 S194L and DSG2 R292C; Case 2: PKP2 2489+1G>A and PKP2 D812N; Case 3: PKP2 M565R and PKP2 D812N) and 1 of digenic heterozygosity (Case 4: PKP2 1728_1729insGATG and DSG2 R292C) among the definite ARVC patients. All family members we investigated have remained asymptomatic. They carried, if any, only a single variant, indicating that the probands carry in <i>trans</i> compound heterozygosity. These results suggest that each of these variants alone may not be sufficient and second variants may be required to manifest overt ARVC in Japanese patients. <b><i>Conclusions:</i></b> Our comprehensive genetic analysis of desmosome genes identified 3 cases of compound heterozygosities in <i>trans</i> and 1 of digenic heterozygosity among 7 definite Japanese ARVC patients, providing novel insights into the genetic basis of Japanese ARVC. (<i>Circ J</i> 2012; <b>76:</b> 737-743)<br>

収録刊行物

  • Circulation journal : official journal of the Japanese Circulation Society

    Circulation journal : official journal of the Japanese Circulation Society 76(3), 737-743, 2012-02-25

    The Japanese Circulation Society

参考文献:  27件中 1-27件 を表示

被引用文献:  2件中 1-2件 を表示

各種コード

  • NII論文ID(NAID)
    10030130444
  • NII書誌ID(NCID)
    AA11591968
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13469843
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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