ATP1A2基因突变所致的偏瘫型偏头痛2例报道

doi:10.3969/j.issn.1674-8115.2022.08.023

上海交通大学学报（医学版） ›› 2022, Vol. 42 ›› Issue (8): 1158-1162.doi: 10.3969/j.issn.1674-8115.2022.08.023

• 病例报告 • 上一篇

ATP1A2基因突变所致的偏瘫型偏头痛2例报道

丁思奇¹^,²(), 黄啸君³, 詹飞霞¹, 田沃土¹, 曹立¹^,²()

^1.上海交通大学医学院附属第六人民医院神经内科，上海 200233
^2.安徽医科大学附属宿州市立医院神经内科，宿州 234000
^3.上海交通大学医学院附属瑞金医院神经内科，神经病学研究所，上海 200025

收稿日期:2022-04-29 接受日期:2022-06-06 出版日期:2022-08-08 发布日期:2022-08-08
通讯作者: 曹立 E-mail:dingsq@rjlab.cn;caoli2000@yeah.net
作者简介:丁思奇（1997—），女，硕士生；电子信箱：dingsq@rjlab.cn。
基金资助:
国家自然科学基金(81870889);上海市教育委员会高峰高原学科建设计划(20161401)

Two cases of hemiplegic migraine caused by ATP1A2 gene mutation

DING Siqi¹^,²(), HUANG Xiaojun³, ZHAN Feixia¹, TIAN Wotu¹, CAO Li¹^,²()

^1.Department of Neurology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
^2.Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou 234000, China
^3.Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received:2022-04-29 Accepted:2022-06-06 Online:2022-08-08 Published:2022-08-08
Contact: CAO Li E-mail:dingsq@rjlab.cn;caoli2000@yeah.net
Supported by:
National Natural Science Foundation of China(81870889);Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20161401)

摘要/Abstract

摘要：

2例患者均幼年起病，主要临床表现为视觉障碍（如视觉闪光点）、偏侧肢体无力、麻木，症状持续约30 min后出现单侧搏动性头痛伴有恶心、呕吐，以上症状在休息后可缓解，不伴其他神经系统疾病。神经系统查体、头颅CT、磁共振成像、脑电图检查和遗传代谢疾病筛查均未见异常。根据《国际头痛疾病分类（第三版）》诊断标准，2例患者符合典型单纯偏瘫型偏头痛的诊断。ATP1A2基因检测显示，2例患者均存在ATP1A2基因突变。病例1为杂合突变c.G2284A/p.G762S，该突变此前报道为致病性突变；病例2为杂合突变c.C3022T/p.R1008W，查阅既往文献及数据库未见该位点单独致病的相关报道。根据美国医学遗传学和基因组学会指南，病例1的ATP1A2基因杂合突变c.G2284A/p.G762S评定为“可能致病”，病例2的ATP1A2基因杂合突变c.C3022T/p.R1008W评定为“意义不明确”。

关键词: 偏瘫型偏头痛, ATP1A2基因, 单纯型, 临床特征

Abstract:

Both 2 cases developed hemiplegic migraine at an early age. The clinical manifestations were almost the same, featuring visual disturbance (such as visual flash) and hemiplegia or hemiparesis. A unilateral pulsating headache with nausea and vomiting developed soon after these auras which lasted about half an hour. The headache was relieved after rest. No abnormality was found in the neurological examination, cranial CT, MRI, electroencephalogram and metabolic disease examination. According to The International Classification of Headache Disorders, 3rd edition (ICHD-3) , both 2 cases were presented as typical pure hemiplegic migraine without other neurological disorders. Genetic sequencing showed ATP1A2 gene mutation in the 2 patients. Heterozygous mutation c.G2284A/p.G762S was present in case 1 and it has previously been shown to be a pathogenic mutation. Case 2 was identified with c.C3022T/p.R1008W, and no related reports were found in the previous literature and databases. According to the standard of American College of Medical Genetics and Genomics (ACMG), c.G2284A/p.G762S in case 1 was as "likely pathogenic" and c.C3022T/p.R1008W in case 2 was as "uncertain significance".

Key words: hemiplegic migraine, ATP1A2, pure phenotype, clinical feature

中图分类号:

R747.2

丁思奇, 黄啸君, 詹飞霞, 田沃土, 曹立. ATP1A2基因突变所致的偏瘫型偏头痛2例报道[J]. 上海交通大学学报（医学版）, 2022, 42(8): 1158-1162.

DING Siqi, HUANG Xiaojun, ZHAN Feixia, TIAN Wotu, CAO Li. Two cases of hemiplegic migraine caused by ATP1A2 gene mutation[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1158-1162.

图/表 1

参考文献 31

1	Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition[J]. Cephalalgia, 2018, 38(1): 1-211.
2	LYKKE THOMSEN L, KIRCHMANN ERIKSEN M, FAERCH ROMER S, et al. An epidemiological survey of hemiplegic migraine[J]. Cephalalgia, 2002, 22(5): 361-375.
3	PELZER N, STAM A H, HAAN J, et al. Familial and sporadic hemiplegic migraine: diagnosis and treatment[J]. Curr Treat Options Neurol, 2013, 15(1): 13-27.
4	RUSSELL M B, DUCROS A. Sporadic and familial hemiplegic migraine: pathophysiological mechanisms, clinical characteristics, diagnosis, and management[J]. Lancet Neurol, 2011, 10(5): 457-470.
5	FERRARI M D, KLEVER R R, TERWINDT G M, et al. Migraine pathophysiology: lessons from mouse models and human genetics[J]. Lancet Neurol, 2015, 14(1): 65-80.
6	TANG W J, ZHANG M C, QIU E C, et al. A Chinese family with familial hemiplegic migraine type 2 due to a novel missense mutation in ATP1A2[J]. Cephalalgia, 2019, 39(11): 1382-1395.
7	RICHARDS S, AZIZ N, BALE S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424.
8	SUTHERLAND H G, ALBURY C L, GRIFFITHS L R. Advances in genetics of migraine[J]. J Headache Pain, 2019, 20(1): 72.
9	THOMSEN L L, OSTERGAARD E, OLESEN J, et al. Evidence for a separate type of migraine with aura: sporadic hemiplegic migraine[J]. Neurology, 2003, 60(4): 595-601.
10	DI STEFANO V, RISPOLI M G, PELLEGRINO N, et al. Diagnostic and therapeutic aspects of hemiplegic migraine[J]. J Neurol Neurosurg Psychiatry, 2020, 91(7): 764-771.
11	CHEN H, SUN X L, WANG R Y, et al. A case report of atypical hemiplegic migraine with nonheadache onset in a Chinese child[J]. BMC Neurol, 2021, 21(1): 267.
12	JEN J C, KLEIN A, BOLTSHAUSER E, et al. Prolonged hemiplegic episodes in children due to mutations in ATP1A2[J]. J Neurol Neurosurg Psychiatry, 2007, 78(5): 523-526.
13	LI Y J, TANG W J, KANG L, et al. Functional correlation of ATP1A2 mutations with phenotypic spectrum: from pure hemiplegic migraine to its variant forms[J]. J Headache Pain, 2021, 22(1): 92.
14	胡笑月, 汤继宏, 奚晓隽, 等. 以发作性意识障碍为主要临床表型的偏瘫型偏头痛(附1例报告及文献复习)[J]. 中国临床神经科学, 2020, 28(6): 649-654.
	HU X Y, TANG J H, XI X J, et al. Hemiplegic migraine presenting with recurrent episodes of impaired consciousness: a case report and literature review [J]. Chin J Clin Neurosci, 2020, 28(6): 649-654.
15	VAN DEN MAAGDENBERG A M, TERWINDT G M, HAAN J, et al. Genetics of headaches[J]. Handb Clin Neurol, 2010, 97: 85-97.
16	DU Y, LI C, DUAN F J, et al. Early treatment in acute severe encephalopathy caused by ATP1A2 mutation of familial hemiplegic migraine type 2: case report and literature review[J]. Neuropediatrics, 2020, 51(3): 215-220.
17	WILBUR C, BUERKI S E, GUELLA I, et al. An infant with epilepsy and recurrent hemiplegia due to compound heterozygous variants in ATP1A2[J]. Pediatr Neurol, 2017, 75: 87-90.
18	SHULL M M, PUGH D G, LINGREL J B. Characterization of the human Na, K-ATPase α2 gene and identification of intragenic restriction fragment length polymorphisms[J]. J Biol Chem, 1989, 264(29): 17532-17543.
19	DE FUSCO M, MARCONI R, SILVESTRI L, et al. Haploinsufficiency of ATP1A2 encoding the Na⁺/K⁺ pump α2 subunit associated with familial hemiplegic migraine type 2[J]. Nat Genet, 2003, 33(2): 192-196.
20	TODT U, DICHGANS M, JURKAT-ROTT K, et al. Rare missense variants in ATP1A2 in families with clustering of common forms of migraine[J]. Hum Mutat, 2005, 26(4): 315-321.
21	BASSI M T, BRESOLIN N, TONELLI A, et al. A novel mutation in the ATP1A2 gene causes alternating hemiplegia of childhood[J]. J Med Genet, 2004, 41(8): 621-628.
22	AMBROSINI A, D'ONOFRIO M, GRIECO G S, et al. Familial basilar migraine associated with a new mutation in the ATP1A2 gene[J]. Neurology, 2005, 65(11): 1826-1828.
23	WANG P, YANG Y R, ZHANG H B, et al. Cognitive dysfunction in a patient with migraine and APT1A2 mutation: a case report[J]. Neurol Sci, 2021, 42(12): 5425-5431.
24	COSTA C, PRONTERA P, SARCHIELLI P, et al. A novel ATP1A2 gene mutation in familial hemiplegic migraine and epilepsy[J]. Cephalalgia, 2014, 34(1): 68-72.
25	BEAUVAIS K, CAVÉ-RIANT F, DE BARACE C, et al. New CACNA1A gene mutation in a case of familial hemiplegic migraine with status epilepticus[J]. Eur Neurol, 2004, 52(1): 58-61.
26	CAPUANI C, MELONE M, TOTTENE A, et al. Defective glutamate and K⁺ clearance by cortical astrocytes in familial hemiplegic migraine type 2[J]. EMBO Mol Med, 2016, 8(8): 967-986.
27	MARTÍNEZ E, MORENO R, LÓPEZ-MESONERO L, et al. Familial hemiplegic migraine with severe attacks: a new report with ATP1A2 mutation[J]. Case Rep Neurol Med, 2016, 2016: 3464285.
28	FRIEDRICH T, TAVRAZ N N, JUNGHANS C. ATP1A2 mutations in migraine: seeing through the facets of an ion pump onto the neurobiology of disease[J]. Front Physiol, 2016, 7: 239.
29	SWEADNER K J, ARYSTARKHOVA E, PENNISTON J T, et al. Genotype-structure-phenotype relationships diverge in paralogs ATP1A1, ATP1A2, and ATP1A3[J]. Neurol Genet, 2019, 5(1): e303.
30	MORTH J P, PEDERSEN B P, TOUSTRUP-JENSEN M S, et al. Crystal structure of the sodium-potassium pump[J]. Nature, 2007, 450(7172): 1043-1049.
31	VGONTZAS A, BURCH R. Episodic migraine with and without aura: key differences and implications for pathophysiology, management, and assessing risks[J]. Curr Pain Headache Rep, 2018, 22(12): 78.

[1]	谢依热·哈木拉提null, 赵倩, 李丞, 宋宁, 王颖, 古丽洁合热·吐尔逊null, 卜军, 杨毅宁, 李晓梅. 基于真实世界的缺血性心脑血管共患疾病的临床特征及卫生经济学评价[J]. 上海交通大学学报（医学版）, 2022, 42(6): 778-785.
[2]	胡佳宁, 张锦文, 刘晓瑞, 陈彩莲, 林羿. 难治性产后出血导致子宫切除的危险因素分析[J]. 上海交通大学学报（医学版）, 2022, 42(4): 409-414.
[3]	黄道, 韦栋, 徐志红, 胡家安. 老年呼吸道病毒感染119例临床特征分析[J]. 上海交通大学学报(医学版), 2021, 41(5): 628-631.
[4]	马银珠，陆光华，钟娜，王海红，和申，赵雪，江海峰，王振. 酒精所致精神病性障碍男性患者临床特征及危险因素[J]. 上海交通大学学报(医学版), 2020, 40(9): 1256-1262.
[5]	祖娟，钱方媛，吴迪，谢新欣，任庆国，张志珺. 成年晚发型糖原贮积症Ⅱ型临床特征及基因突变分析[J]. 上海交通大学学报(医学版), 2020, 40(8): 1108-1112.
[6]	曾素，许培培，郭明高. 具有乳头样核特征的非浸润性甲状腺滤泡性肿瘤的临床研究进展[J]. 上海交通大学学报(医学版), 2020, 40(7): 968-973.
[7]	吕娜，叶惠玲，范青#，肖泽萍#. 伴囤积症状强迫症患者的临床特征研究[J]. 上海交通大学学报(医学版), 2020, 40(6): 791-797.
[8]	管红艳，刘婧娴，刘瑛. 分离自血培养肺炎克雷伯菌的毒力基因及患者临床特征分析[J]. 上海交通大学学报（医学版）, 2020, 40(2): 235-.
[9]	姜涛 1, 2，施晴 1，许彭鹏 1，程澍 1，王黎 1，赵维莅 1. 肾上腺淋巴瘤临床病理特点及预后因素分析[J]. 上海交通大学学报（医学版）, 2019, 39(9): 1032-.
[10]	陈珺珏，田琳璐，韦严，亢晓丽. X染色体连锁显性遗传婴儿眼球震颤家系的临床特征研究[J]. 上海交通大学学报（医学版）, 2018, 38(11): 1355-.
[11]	宋亚兰，罗玲，张运芝. 肝硬化失代偿期患者并发肠梗阻的临床特点及相关危险因素分析[J]. 上海交通大学学报（医学版）, 2017, 37(7): 993-.
[12]	朱琦,姜瑛，于颖彦,黄霞 . 2005—2014 年瑞金医院胃恶性肿瘤临床及病理学特征分析[J]. 上海交通大学学报（医学版）, 2017, 37(7): 1025-.
[13]	周儒白，洪武，赵国庆，黄佳，粟幼嵩，王勇，胡莺燕，曹岚，苑成梅，彭代辉，吴志国，汪作为，邢梦娟，陈俊，方贻儒 . 首次躁狂发作患者不同亚型临床特征分析[J]. 上海交通大学学报（医学版）, 2017, 37(4): 490-.
[14]	田李均，王晓丽，肖淑珍，孙景勇，刘嘉琳，瞿洪平. 医院内高黏液性肺炎克雷伯菌的流行分布、毒力基因及临床特征分析[J]. 上海交通大学学报（医学版）, 2017, 37(1): 43-.
[15]	肖慧芳郝杰赵维莅王黎. 非霍奇金淋巴瘤合并噬血细胞综合征的临床与预后分析[J]. 上海交通大学学报（医学版）, 2016, 36(8): 1187-.

ATP1A2基因突变所致的偏瘫型偏头痛2例报道

Two cases of hemiplegic migraine caused by ATP1A2 gene mutation

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 1

参考文献 31

相关文章 15

编辑推荐

Metrics