ANXA11基因突变的额颞叶痴呆一例并文献复习

Frontotemporal dementia with ANXA11 gene mutation:a case report and literature review

目的报道1例以对视交流时不能抑制的大笑为主要表现的额颞叶痴呆(FTD)患者的临床表现和基因特点。方法分析1例2019年10月18日就诊于首都医科大学宣武医院的FTD患者的临床表现、影像学特征,收集患者脑脊液、正电子发射断层摄影术-电子计算机体层扫描(PET-CT)、单光子发射计算机断层扫描等检查资料,并对患者血液标本进行FTD相关基因检测。结果该患者为66岁女性,隐袭起病,症状逐渐进展,突出表现为与人对视交流时难以控制的大笑,有幼稚、固执等性格变化,有兴趣丧失、易激动等情绪变化,同时有轻微行动迟缓、语速变慢、言语含混等运动及语言障碍。头颅磁共振成像示双侧额颞叶、双侧海马萎缩;PET-CT脑代谢显像示双侧额顶颞叶、海马、枕叶代谢不同程度减低,右侧为著。最终诊断为行为变异型FTD。额颞叶相关基因检测发现该患者存在肌萎缩侧索硬化(ALS)致病基因ANXA11基因c.107C>G(p.P36R)突变。结论这是第1例在单纯FTD中发现ALS致病基因ANXA11基因杂合突变的病例,提示ANXA11基因有可能在FTD发病机制中具有重要意义,也进一步支持ALS与FTD为谱系疾病的学说。

Objective To report a case with frontotemporal dementia (FTD) characterized by involuntary laughter.MethodsThe clinical manifestations and imaging characteristics of a patient diagnosed as FTD was analyzed. Then the results of cerebrospinal fluid, positron emission tomography-computed tomography (PET-CT) and single-photon emission computed tomography examinations were collected. Blood samples were tested for related genes of FTD.Results The patient is a 66 years old woman with insidious onset and progressing symptoms and she was mainly manifested as laughing out loud involuntarily when looking at others, childishness, stubbornness, loss of interest, irritability and other personal changes. Mild motor and language disorders were also manifested as moving slowly and speaking unclearly. The magnetic resonance imaging showed the atrophy of bilateral frontal, temporal lobe and bilateral hippocampal while the image of PET-CT showed the metabolism was reduced in different degrees. Eventually, behavioural variant of FTD was diagnosed. The result of ANXA11 gene sequencing revealed the mutation of c.107C>G(p.P36R).Conclusions This is the first case in which a heterozygous mutation of ANXA11 gene, which is related to amyotrophic lateral sclerosis (ALS), is found in simple FTD patient, suggesting that ANXA11 gene may play an important role in the pathogenesis of FTD. This further supports the theory that ALS and FTD are spectrum disorders.