ABCC9 缺陷导致 CMD10、ATFB12 和坎图综合征
中文名称
通路描述
ABCC9 是 ATP 结合型 C 亚家族成员 9，与 ATP 敏感内向整流钾通道 11 (KCNJ11) 形成心脏和平滑肌型 KATP 通道。KCNJ11 形成通道孔，而 ABCC9 对激活和调节是必需的。内向整流钾通道倾向于将钾离子流入细胞而非流出。KATP 通道对细胞内 ADP/ATP 比率的变化开放和关闭，从而将细胞的代谢状态与其膜电位联系起来。抑制 KATP 通道活性导致膜去极化，进而激活电压依赖性 Ca2+ 通道，导致 Ca2+ 内流和细胞内 Ca2+ 浓度升高。钙离子的正确平衡对于心脏的正常功能至关重要。ABCC9 缺陷可导致扩张型心肌病 10 (CMD10)，其特征为室壁扩张和收缩功能受损，导致心力衰竭和心律失常。ABCC9 缺陷还可导致家族性心房颤动 12 (ATFB12)，其特征为心房电活动紊乱和无效的心房收缩，导致心房血液淤滞，并减少心室充盈。这可能导致心悸、晕厥、血栓栓塞性中风和心力衰竭。ABCC9 缺陷还可导致多毛性骨软骨发育不良 (坎图综合征)，这是一种罕见的疾病，其特征为先天性多毛症、新生儿巨大儿、独特的骨软骨发育不良和心脏肥大。
英文描述
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome ATP-binding cassette sub-family C member 9 (ABCC9) forms cardiac and smooth muscle-type KATP channels with ATP-sensitive inward rectifier potassium channel 11 (KCNJ11). KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation (Babenko et al. 1998, Tammaro & Ashcroft 2007). Inward rectifier potassium channels favor the flow of potassium into the cell rather than out of it. KATP channels open and close in response to intracellular changes in the ADP/ATP ratio, thereby linking the metabolic state of the cell to its membrane potential. Inhibition of KATP channel activity causes membrane depolarization and thereby activation of voltage-dependent Ca2+ channels, leading to Ca2+ influx and a rise in intracellular Ca2+ concentration. Correct maintenance of calcium balance is essential for the normal functioning of the heart.
Defects in ABCC9 can cause dilated cardiomyopathy 10 (CMD10: MIM:608569), a disorder characterised by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia (Bienengraeber et al. 2004). Defects in ABCC9 can also cause familial atrial fibrillation 12 (ATFB12; MIM:614050), characterised by disorganized atrial electrical activity and ineffective atrial contraction resulting in blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure (Olson et al. 2007). Defects in ABCC9 can also cause hypertrichotic osteochondrodysplasia (Cantu syndrome; MIM:239850), a rare disorder characterised by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia and cardiomegaly (van Bon et al. 2012, Harakalova et al. 2012).
Defects in ABCC9 can cause dilated cardiomyopathy 10 (CMD10: MIM:608569), a disorder characterised by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia (Bienengraeber et al. 2004). Defects in ABCC9 can also cause familial atrial fibrillation 12 (ATFB12; MIM:614050), characterised by disorganized atrial electrical activity and ineffective atrial contraction resulting in blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure (Olson et al. 2007). Defects in ABCC9 can also cause hypertrichotic osteochondrodysplasia (Cantu syndrome; MIM:239850), a rare disorder characterised by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia and cardiomegaly (van Bon et al. 2012, Harakalova et al. 2012).
所含基因
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