Case report: A novel loss-of-function pathogenic variant in the KCNA1 cytoplasmic N-terminus causing carbamazepine-responsive type 1 episodic ataxia.
Case report: A novel loss-of-function pathogenic variant in the KCNA1 cytoplasmic N-terminus causing carbamazepine-responsive type 1 episodic ataxia.
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DOI：
10.3389/fneur.2022.975849
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发表时间：
2022
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
--
作者：
发作性共济失调是一组神经系统疾病的总称，这些疾病会对运动产生不利和间歇性影响。癫痫是复发性的，其特征是失去平衡和协调，并可伴有从恶心到偏瘫的其他症状。发作性共济失调1型（EA 1）是一种遗传性常染色体显性遗传疾病，由编码电压门控钾通道KCNA 1（Kv1.1）的KCNA 1序列变异引起。在这里，我们报告了一种新的功能丧失型KCNA 1致病变异[c.464T>C/p.Leu155Phe]，导致年轻女性先证者频繁、突然出现笨拙或蹒跚步态。这种基因变异是母系遗传的，母亲的症状也始于童年，MRI和EEG正常，言语不清，上肢和口腔运动障碍。母亲和女儿都对卡马西平有反应。KCNA 1-L155 P钾通道的细胞电生理学研究显示，杂合通道中的功能完全但非显性丧失，电流降低，门控改变。据我们所知，这是第一个位于KCNA 1胞质N-末端的EA 1相关致病性变体，扩大了已报道的该通道的临床敏感域。
Episodic ataxia is an umbrella term for a group of nervous system disorders that adversely and episodically affect movement. Episodes are recurrent, characterized by loss of balance and coordination and can be accompanied by other symptoms ranging from nausea to hemiplegia. Episodic Ataxia Type 1 (EA1) is an inherited, autosomal dominant disease caused by sequence variants in KCNA1, which encodes the voltage-gated potassium channel, KCNA1 (Kv1.1). Here we report a novel loss-of-function KCNA1 pathogenic variant [c.464T>C/p.Leu155Phe] causing frequent, sudden onset of clumsiness or staggering gait in the young female proband. The gene variant was maternally inherited and the mother, whose symptoms also began in childhood, has a normal MRI and EEG, slurred speech and dystonic movements involving upper extremities and mouth. Both mother and daughter are responsive to carbamazepine. Cellular electrophysiology studies of KCNA1-L155P potassium channels revealed complete but non-dominant loss of function, with reduced current and altered gating in heterozygous channels. To our knowledge this is the first EA1-associated pathogenic variant located in the KCNA1 cytoplasmic N-terminus, expanding the reported clinically sensitive domains of the channel.
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影响因子：
5.3
作者：
D'Adamo MC;Hasan S;Guglielmi L;Servettini I;Cenciarini M;Catacuzzeno L;Franciolini F
通讯作者：
Franciolini F
影响因子：
4.6
作者：
Pliego, Jessica Abigail Feria;Pedroarena, Christine M.
通讯作者：
Pedroarena, Christine M.
影响因子：
3.5
作者：
Jodice, C;Mantuano, E;Frontali, M
通讯作者：
Frontali, M
影响因子：
30.8
作者：
BROWNE, DL;GANCHER, ST;LITT, M
通讯作者：
LITT, M
影响因子：
16.2
作者：
Goldberg, Ethan M.;Clark, Brian D.;Rudy, Bernardo
通讯作者：
Rudy, Bernardo