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突発性乳児死亡症候群における,骨格筋の電圧ゲート型ナトリウムチャネルであるNaV1. 4の機能障害:症例対照研究
Roope Männikkö1, Leonie Wong2, David J Tester3
1MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, University College London, London, UK.
Lancet (London, England)
|April 2, 2018
まとめ
ナトリウムチャネル NaV1. 4 に影響する希少な SCN4A 遺伝子変異は,突然乳児死亡症候群 (SIDS) で死亡した乳児で発見されました. これは,SCN4A変種とSIDSのリスクとの潜在的な関連を示唆しています.
科学分野:
- 遺伝学
- 神経学
- 小児科
背景:
- 急性 幼児 死亡 症候群 (SIDS) は,高所得 国 で の 幼児 死亡 の 主要 な 原因 で ある.
- 中枢呼吸器機能障害は SIDS に関与しています
- SCN4A遺伝子は,骨格筋の刺激と呼吸機能に不可欠なNaV1. 4ナトリウムチャネルをコードする.
研究 の 目的:
- SIDSで死亡した乳児では,希少で機能的に破壊的なSCN4A変種が過剰に存在するという仮説を調査する.
- SIDSの病理生理学におけるSCN4Aの潜在的な役割を調査する.
主な方法:
- 278人のSIDS症例と729人の民族的にマッチした対照群を対象とした症例対照研究です.
- SIDS症例と対照群の間の希少なSCN4A変異の頻度 (マイナーアレル頻度<0·00005) の比較
- 異種表現システムを用いた変種チャネルの生体物理的特徴化.
主要な成果:
- 4人 (1. 4%) のSIDSの乳児は,希少で機能障害のあるSCN4Aの変異体を持っていた.
- コントロールの乳児 (0%) はそのような変異体を持っていなかった (p=0. 0057).
結論:
- NaV1. 4の機能を変化させる希少なSCN4A変異はSIDSと関連しています.
- これらの変異は筋肉の興奮性を低下させ,呼吸器や喉頭機能を損なう可能性があると予測されています.
- SCN4A機能不全は,SIDS症例のサブセットにおいて,潜在的に修正可能なリスク因子です.
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