超長鎖アシル-CoA脱水素酵素欠乏症における分子異質性は,小児性心筋病と突然死を引き起こす
A Mathur1, H F Sims, D Gopalakrishnan
1Departments of Pediatrics, Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis Children's Hospital, St Louis, MO, USA.
Circulation
|March 17, 1999
まとめ
非常に長い鎖のアシル-コア脱水素酵素 (VLCAD) の遺伝的欠陥は,幼児心筋病を引き起こす. 往々にして致命的ですが,VLCAD欠乏症と心臓の問題は治療で回復します.
科学分野:
- 遺伝学 遺伝学とは
- メタボリック障害 メタボリック障害
- 心臓病学 心臓病学
背景:
- 原発性心筋症 (CM) は,遺伝的欠陥とますます結びついている.
- 超長鎖アシル-コア脱水素酵素 (VLCAD) は,脂肪酸のβ酸化による心臓のエネルギー生成に不可欠である.
研究 の 目的:
- 心筋病と脂肪酸酸化障害の特徴を示す患者のVLCAD遺伝子変異の役割を調査する.
主な方法:
- シングル・ストランド・コンフォーメーション・ヴァリアンス分析を用いたゲノムDNAのスクリーニング.
- VLCAD遺伝子のDNAシーケンシングと変異分析を行いました.
- RNAブラット分析とVLCAD酵素アッセイを用いた.
主要な成果:
- 18人の患者で21の異なるVLCAD遺伝子変異を特定し,80%がCMに関連していました.
- 乳幼児の重度のCM (67%) と肝機能障害 (33%) が一般的な症状でした.
- フレームシフトまたはスプライスサイト変異により,VLCAD mRNAと酵素活性が低下しました.
結論:
- 乳児性心筋症は,VLCAD欠乏症の主要な臨床的表れである.
- VLCAD遺伝子変異は多様です.
- VLCAD欠乏症に関連した代謝障害と心筋病は,初期死亡率が高いにもかかわらず,両方を逆転させることができます.
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