<i>GFAP</i>基因c.1249delG变异引起的婴儿型亚历山大病1例

赖盼建; 王大燕; 李小兵

doi:10.16766/j.cnki.issn.1674-4152.002619

GFAP基因c.1249delG变异引起的婴儿型亚历山大病1例

doi: 10.16766/j.cnki.issn.1674-4152.002619

金华市妇幼保健院，浙江金华 321000

基金项目:

浙江省医药卫生科技计划项目 2020KY342

详细信息

通讯作者:
王大燕, E-mail: airy005@163.com

中图分类号: R742.8
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出版历程
- 收稿日期: 2021-06-20

A case report of infantile Alexander disease caused by GFAP gene c.1249delG mutation

Jinhua Maternal and Child Health Care Hospital, Jinhua, Zhejiang 321000, China

摘要

摘要: 探讨婴儿型亚历山大病的遗传性特征。对原因不明的反复抽搐、合并脑白质异常的患者进行高通量测序全外显组测序，筛选出致病基因，最后通过Sanger测序在家系成员中验证基因突变。结果在患者中检测到GFAP基因变异c.1249delG（p.Asp417MetfsTer15）。提示GFAP基因c.1249delG的变异可以引起中国人婴儿型亚历山大病。
- 亚历山大病 /
- 基因变异 /
- 婴儿型
Abstract: To discuss genetic characteristics of infantile Alexandria disease. Patients with unexplained repeated convulsions and abnormal white matter were subjected to high-throughput sequencing and full-exome sequencing to screen for pathogenic genes. Finally, gene mutations were verified in family members by Sanger sequencing. A GFAP gene mutation c.1249delG (p.Asp417MetfsTer15) was detected in patients. It indicates that the GFAP gene c.1249delG mutation can cause infantile Alexandria disease in Chinese.
- Braden scale /
- Pressure injury /
- Prevention
利益冲突 无

HTML全文

图 1 患儿头颅MRI及脑电图

注：头颅MRI提示两侧广泛、对称性脑白质病变，A、B为T₂加权像，C为T₁加权像；D为脑电图可见痫样放电，左侧明显(箭头所示)。

Figure 1. Brain MRI and electroencephalogram

下载: 全尺寸图片幻灯片

图 2 先证者及其父母GFAP基因变异Sanger测序验证结果示意图

Figure 2. Proband and parents GFAP gene variants schematic Sanger sequencing the results of the validation

下载: 全尺寸图片幻灯片

参考文献(17)

[1]	VÁZQUEZ E, MACAYA A, MAYOLAS N, et al. Neonatal Alexander disease: MR imaging prenatal diagnosis[J]. AJNR Am J Neuroradiol, 2008, 29(10): 1973-1975. doi: 10.3174/ajnr.A1215
[2]	孙云闯, 黄一宁, 朱慧, 等. GFAP基因新突变致罕见表现的亚历山大病临床及基因突变分析[J]. 中国现代神经疾病杂志, 2019, 19(3): 199-204. SUN Y C, HUANG Y N. Clinical and gene mutation analysis on Alexander's disease type Ⅱ caused by a novel GFAP mutation[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2019, 19(3): 199-204.
[3]	JOHNSON A B, BRENNER M. Alexander's disease: Clinical, pathologic, and genetic features[J]. J Child Neurol, 2003, 18(9): 625-632. doi: 10.1177/08830738030180090901
[4]	夏晓娜, 董影, 叶春涛, 等. 亚历山大病一例[J]. 临床放射学杂志, 2016, 35(10): 1540-1541. doi: 10.13437/j.cnki.jcr.2016.10.023 XIA X N, DONG Y, YE C T, et al. A case of Alexander's disease[J]. Journal of Clinical Radiology, 2016, 35(10): 1540-1541. doi: 10.13437/j.cnki.jcr.2016.10.023
[5]	HAYASHI Y, NAGASAWA M, ASANO T, et al. Central hypothermia associated with Alexander disease. A case report[J]. Clin Neurol Neurosurg, 2017, 157: 31-33. doi: 10.1016/j.clineuro.2017.03.013
[6]	班婷婷, 吴晔, 张仲斌, 等. 亚历山大病Ⅱ型4例临床及文献复习[J]. 中华实用儿科临床杂志, 2016, 31(9): 700-705. doi: 10.3760/cma.j.issn.2095-428X.2016.09.015 BAN T T, WU Y, ZHANG Z B, et al. Clinical research of 4 patients with type Ⅱ Alexander disease and literature review[J]. Chinese Journal of Applied Clinical Pediatrics, 2016, 31(9): 700-705. doi: 10.3760/cma.j.issn.2095-428X.2016.09.015
[7]	LIU Y H, ZHOU H, WANG H B, et al. Atypical MRI features in familial adult onset Alexander disease: Case report[J]. BMC Neurol, 2016, 16(1): 211. doi: 10.1186/s12883-016-0734-9
[8]	MESSING A, LAPASH DANIELS C M, HAGEMANN T L. Strategies for treatment in Alexander disease[J]. Neurotherapeutics, 2010, 7(4): 507-515. doi: 10.1016/j.nurt.2010.05.013
[9]	REMSTER E, DUBEY D. Considering spastic paraplegia type 7 and adult-onset Alexander disease-reply[J]. JAMA Neurol, 2017, 74(7): 869.
[10]	YOSHIDA T, YASUDA R, MIZUTA I, et al. Quantitative evaluation of brain stem atrophy using magnetic resonance imaging in adult patients with Alexander disease[J]. Eur Neurol, 2017, 77(5-6): 296-302. doi: 10.1159/000475661
[11]	GARCIA-REITBOECK P, MACKINNON ANDREW D, MCENTAGART M, et al. Prominent cognitive decline and behavioural disturbance in late-onset Alexander disease[J]. J Neurol Sci, 2015, 357(1-2): 319-321. doi: 10.1016/j.jns.2015.07.038
[12]	VAN DER KNAAP M S, SALOMONS G S, LI R, et al. Unusual variants of Alexander's disease[J]. Ann Neurol, 2005, 57(3): 327-338. doi: 10.1002/ana.20381
[13]	MURAKAMI N, TSUCHIYA T, KANAZAWA N, et al. Novel deletion mutation in GFAP gene in an infantile form of Alexander disease[J]. Pediatr Neurol, 2008, 38(1): 50-52. doi: 10.1016/j.pediatrneurol.2007.08.017
[14]	FLINT D, LI R, WEBSTER L S, et al. Splice site, frameshift, and chimeric GFAP mutations in Alexander disease[J]. Hum Mutat, 2012, 33(7): 1141-1148. doi: 10.1002/humu.22094
[15]	CHEN Y S, LIM S C, CHEN M H, et al. Alexander disease causing mutations in the C-terminal domain of GFAP are deleterious both to assembly and network formation with the potential to both activate caspase 3 and decrease cell viability[J]. Exp Cell Res, 2011, 317(16): 2252-2266. doi: 10.1016/j.yexcr.2011.06.017
[16]	GÓMEZ-PINEDO U, DURAN-MORENO M, SIREROL-PIQUER S, et al. Myelin changes in Alexander disease science direct[J]. Neurología, 2018, 33(8): 526-533. doi: 10.1016/j.nrl.2017.01.019
[17]	韩崔莹, 冯歆珂, 李晓波, 等. GFAP基因杂合突变致Ⅱ型亚历山大病的相关临床、影像及基因突变分析1例报告[J]. 中风与神经疾病杂志, 2019, 36(8): 751-752. https://www.cnki.com.cn/Article/CJFDTOTAL-ZFSJ201908021.htm HAN C Y, FENG X K, LI X B, et al. GFAP heterozygous mutations related to type Ⅱ Alexander disease clinical, imaging and gene mutation analysis report in 1 case[J]. Journal of Apoplexy and Nervous Diseases, 2019, 36(8): 751-752. https://www.cnki.com.cn/Article/CJFDTOTAL-ZFSJ201908021.htm