CSF1R基因新位点突变所致的伴球状体遗传性弥漫性白质脑病1例  

A report of 1 case with hereditary diffuse leukoencephalopathy with spheroids(HDLS)due to a new mutation of colony-stimulating factor 1 receptor(CSF1R)

作　　者：谢乐静[1] 陈淳淳 马英 朱飞奇 XIE Le-jing;CHEN Chun-chun;MA Ying;ZHU Feiqi(Department of General practice,Luohu People’s Hosptial,Shenzhen,518001,China)

机构地区：[1]深圳市罗湖区人民医院综合科,深圳518001 [2]深圳市罗湖区人民医院神经内科/老年病分院老年性认知障碍病房,深圳518001 [3]深圳市罗湖区人民医院心内科,深圳518001

出　　处：《阿尔茨海默病及相关病杂志》2020年第3期195-198,共4页Chinese Journal of Alzheimer's Disease and Related Disorders

基　　金：深圳市政府医疗卫生三名工程项目“瑞典卡罗琳斯卡医学院NVS系Bengt Winblad教授阿尔茨海默病团队”资助(SZSM201801014)。

摘　　要：伴球状体遗传性弥漫性白质脑病(hereditary diffuse leukoencephalopathy with spheroids,HDLS)是临床罕见疾病,容易误诊为阿尔茨海默病、额颞叶痴呆、帕金森综合征、多发性硬化、抑郁症甚至脑梗塞。HDLS病情进展快,预后极差。HDLS的致病基因主要位于集落刺激因子1受体(colony stimulating factor 1 receptor gene,CSF1R)基因的12号至22号外显子杂合突变,导致高度保守的酪氨酸激酶结构域功能异常。目前国内只有个别案例报道HDLS病例,我们收治1例经过全外显子测序确诊的病例,该患者为68岁女性患者,58岁时开始出现记忆力下降和动作不协调,曾被诊断为阿尔茨海默病,予以多奈哌齐和美金刚治疗无效,病情持续进展,发病第5年开始出现癫痫大发作,予以德巴金治疗,发病第7年出现失语和行走不能、卧床、不认识家人、尿失禁等,2020年1月因癫痫频繁发作来我院住院,查头颅MRI发现双侧大脑半球对称性脑白质异常信号和萎缩、侧脑室扩大和脑萎缩。通过全外显子测序证实为CSF1R第3号外显子c.220G>A(鸟嘌呤>腺嘌呤),导致氨基酸改变p.A74T(丙氨酸>苏氨酸)。根据HGMDpro数据库报道情况:该突变位点c:220G>A未见报道。父母目前90岁仍健在,无痴呆家族史,兄妹及子女健康,但是家属拒绝检测该基因,患者直系亲属CSF1R基因突变携带情况不清,故该患者可能为散发性CSF1R基因3外显子基因突变所致HDLS。2016年Brain杂志和2019年JNNP杂志的个案报道发现异体造血干细胞移植治疗对HDLS病情的改善和稳定有效,因此提高对本病的认识,及早开展异体造血干细胞移植治疗对改善患者预后具有非常重要的意义。Hereditary diffuse leukoencephalopathy with spheroids(HDLS)is a rare disease,which is very easy to be misdiagnosis as Alzheimer’s disease,frontotemporal demention,Parkinson’s syndrome,multiple sclerosis,depression and ischemic stroke etc.The progress of HDLS is very quick and its prognosis is very severe.The etiology of HDLS is the mutation of colony stimulating factor 1 receptor gene in exon 12-22.At present,only a few cases of HDLS have been reported in China.Here we reported a case with HDLS who was a 68 year old female.At the age of 58,she began to have memory decline and movement discordance.She had been once diagnosed with Alzheimer’s disease and accepted the treatments of donepezil and memantine.Her disease continued to progress.In the fifth year,she began to have generalized seizures and accepted the treatment of sodium valproate.In the 7th year,she suffered with aphasia,walking disability,bedridden,family unknown,urinary incontinence,etc.In January 2020,due to frequent seizures,She were hospitalized in Luohu People’s Hospital.We found that her bilateral cerebral hemispheres had symmetrical abnormal signals and atrophy of white matter,enlargement of lateral ventricle and atrophy of brain by the brain magnetic resonance image(MRI).It was confirmed that she has a mutation in exon 3 of CSF1R(c.220g>A(guanine>adenine),p.a74t(alanine>threonine))by whole exon gene sequencing.According to HGMDpro database,this mutation has not been reported.At present,her parents are still alive at the age of 90,without family history of dementia,and the siblings and children are healthy.However,the family refuses to detect the gene.The mutation of CSF1R gene in her immediate relatives is unclear,so she may be a HDLS patient caused by the mutation of exon 3 gene of CSF1R.It had been reported that the treatment of allogeneic hematopoietic stem cell transplantation is effective for the improvement and stability of HDLS,so it is very important to improve the understanding of the disease and carry out allogeneic hematopoieti

关 键 词：伴球状体遗传性弥漫性白质脑病 集落刺激因子1R 3号外显子 

分 类 号：R741.04[医药卫生—神经病学与精神病学]