Genotype-phenotype correlations in alternating hemiplegia of childhood
Genotype-phenotype correlations in alternating hemiplegia of childhood
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DOI：
10.1212/wnl.0000000000000102
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发表时间：
2014-02-11
期刊：
影响因子：
9.9
通讯作者：
Hirose, Shinichi
中科院分区：
文献类型：
--
作者：
Sasaki, Masayuki;Ishii, Atsushi;Hirose, Shinichi
目的：儿童交替性偏瘫 (AHC) 的临床严重程度差异很大。为了探讨AHC基因型-表型相关性，我们分析了AHC患者的临床信息和ATP1A3突变。方法：35名临床诊断为AHC的日本患者参与了本研究。使用桑格测序分析 ATP1A3 突变。从 AHC 患者家属和负责其护理的临床医生收集了详细的临床信息。结果：基因分析显示 33 例患者存在 ATP1A3 新生杂合错义突变：Glu815Lys 12 例（36%），Asp801Asn 10 例（30%），其他错义突变 11 例。比较了 Glu815Lys、Asp801Asn 和其他突变组的临床信息。统计分析显示，Glu815Lys组的新生儿发病史、粗大运动水平、癫痫持续状态和呼吸麻痹与其他组相比存在显着差异。此外，8名未接受氟桂利嗪治疗的患者出现了严重的运动恶化。结论：Glu815Lys基因型似乎与最严重的AHC表型相关。尽管 AHC 通常不被视为一种进行性疾病，但应将其视为一种突然恶化或逐步恶化的疾病，特别是在具有 Glu815Lys 突变的患者中。
Objective:Clinical severity of alternating hemiplegia of childhood (AHC) is extremely variable. To investigate genotype-phenotype correlations in AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC.Methods:Thirty-five Japanese patients who were clinically diagnosed with AHC participated in this study. ATP1A3 mutations were analyzed using Sanger sequencing. Detailed clinical information was collected from family members of patients with AHC and clinicians responsible for their care.Results:Gene analysis revealed 33 patients with de novo heterozygous missense mutations of ATP1A3: Glu815Lys in 12 cases (36%), Asp801Asn in 10 cases (30%), and other missense mutations in 11 cases. Clinical information was compared among the Glu815Lys, Asp801Asn, and other mutation groups. Statistical analysis revealed significant differences in the history of neonatal onset, gross motor level, status epilepticus, and respiratory paralysis in the Glu815Lys group compared with the other groups. In addition, 8 patients who did not receive flunarizine had severe motor deteriorations.Conclusions:The Glu815Lys genotype appears to be associated with the most severe AHC phenotype. Although AHC is not generally seen as a progressive disorder, it should be considered a disorder that deteriorates abruptly or in a stepwise fashion, particularly in patients with the Glu815Lys mutation.