【摘要】 目的：报道1例首诊为脑炎的不完全型Wolfram综合征（Wolfram syndrome, WS）病例。方法：对1例因头痛、言语困难伴记忆力下降5个月的患者应用目标区域捕获高通量测序进行全外显子测序。收集其临床资料并结合基因测序结果进行文献复习。结果：患者41岁，男性，因头痛、言语困难伴记忆力下降5个月入院，既往糖尿病、偏头痛、高度近视、耳聋病史。5个月前突发言语困难，不能交流，颅脑MRI检查提示左侧颞叶、岛叶、顶叶DWI高信号，疑诊为脑炎，遗传代谢病不能排除，完善传染病、自身免疫性脑炎、乳酸、风湿、甲状腺功能等检查，全外显子测序提示WFS1基因外显子8中有1个突变，c.975C>A，经SIFT软件预测该突变为Affect protein function，经Polyphen-2软件预测该突变为Probably damaging。美国医学遗传学与基因组学学会（ACMG）证据显示该位点临床意义未明。对其姑姑、妹妹、舅舅及姨妈进行的家系验证发现其舅舅及姨妈与患者突变位点一致。患者影像学未见明显视神经、脑干及小脑萎缩，与多数文献报道不同。结论：临床表现为脑炎样发作的WS较少见，对于有多系统累及的患者，除考虑免疫、代谢、肿瘤等相关病因外，相对罕见的遗传性疾病也应纳入鉴别诊断。更多还原

【Abstract】 Objective: To report a case of atypical Wolfram syndrome(WS) presenting with encephalitis as the initial symptom.Methods: We conducted targeted region capture high-throughput sequencing for whole exome sequencing in a patient who presented with a 5-month history of headache, speech difficulties, and memory decline. Clinical data were collected, and the genetic sequencing results were reviewed in conjunction with relevant literature. Results:A 41-year-old male patient with a history of diabetes, migraines, high myopia, and hearing loss was admitted due to a 5-month history of headache, speech difficulties, and memory decline. Five months prior, he experienced sudden speech difficulties and inability to communicate. Brain MRI revealed high signal intensity on diffusion-weighted imaging(DWI) in the left temporal, insular, and parietal lobes, raising suspicion of encephalitis. Genetic metabolic disorders were considered, and further investigations were conducted for infectious diseases, autoimmune encephalitis, lactate levels, rheumatological markers, and thyroid function. Whole exome sequencing revealed a mutation in exon 8 of the WFS1 gene, specifically c.975C>A. In silico analysis using SIFT predicted this mutation to affect protein function, and Polyphen-2 predicted it as probably damaging. The American College of Medical Genetics and Genomics(ACMG)guidelines indicated that the clinical significance of this variant is uncertain. Familial verification involving the patient’s aunt, sister, uncle, and maternal aunt revealed concurrence of the mutation with the patient’s uncle and maternal aunt. Unlike most reported literature, the patient’s imaging did not display significant optic nerve, brainstem, or cerebellar atrophy. Conclusion: Atypical presentations of WS as encephalitis-like episodes are rare. In patients with multisystem involvement, in addition to considering immunological, metabolic, and neoplastic causes, rare hereditary conditions should also be considered.更多还原