Abstract:

Objective To report the clinical phenotype and genetic characteristics of an Alexander's disease type Ⅱ patient with unusual presentation, so as to extend phenotype and gene mutation spectrum of Alexander's disease type Ⅱ. Methods and Results A 41-year-old male patient suffered from paroxysmal right limb stiffness for 10 years, presenting with spastic hemiparesis on right side and bilateral pyramidal tract sign. Brain MRI showed long T₂ signal in bilateral medulla, bulbar-pontine junction and the upper cervical spinal cord, as well as mild demyelination in bilateral periventricular white matter. Steroid pulse therapy was invalid. Antiepileptic drugs (AEDs) were partially effective. Genetic analysis showed one heterozygous deletion of glial fibrillary acidic protein (GFAP) gene [c.del 1044-1079 GTACCAGGACCTGCTCAATGTCAAGCTGGCCCTGGA (p.E348DdelY349-D360)] in the proband and his mother. This mutation has not been reported before. The patient was clearly diagnosed as Alexander's disease type Ⅱ, and his family was diagnosed as Alexander's disease type Ⅱ pedigree. Conclusions The novel mutation of GFAP gene expanded the gene mutation spectrum of Alexander's disease. The clinical phenotypes of family members may be variable even in the same family.

Key words: Alexander disease, Movement disorders, Glial fibrillary acidic protein, Genes, Mutation, Pedigree

摘要：

目的 报道 1 例临床罕见的Ⅱ型亚历山大病病例，总结临床表型和基因型特征，扩展Ⅱ型亚历山大病临床表型和基因突变谱。方法与结果 男性患者，41 岁，发作性右侧肢体僵硬10年，表现为右侧痉挛性偏瘫步态、双侧锥体束征；头部 MRI可见双侧延髓、延髓脑桥交界区和上颈髓呈长T₂ 信号影，双侧侧脑室旁白质轻度脱髓鞘；激素冲击治疗无效，抗癫 药物部分有效。基因检测患者及其母存在胶质纤维酸性蛋白（GFAP）基因杂合性缺失突变［c.del 1044 ~ 1079 GTACCAGGACCTGCTCAATGTCAAGCTGGCCCTGGA（p.E348DdelY349 ~ D360）］，为新发突变。明确诊断为Ⅱ型亚历山大病，该家系证实为Ⅱ型亚历山大病家系。结论 GFAP 基因缺失突变为新发突变，扩大了Ⅱ型亚历山大病的基因突变谱。同一家系中不同患者的临床表型差异较大。

关键词:  Alexander病, 运动障碍, 神经胶质原纤维酸性蛋白质, 基因, 突变, 系谱