LMNB1相关常染色体显性遗传成人型脑白质营养不良家系分析  

A pedigree analysis of LMNB1-related adult-onset autosomal dominant leukodystrophy

作　　者：宋先红 王占军 宋旸[1] 王宪玲[1] 李旭颖[1] 王朝东[1] 李存江[1] Song Xianhong;Wang Zhanjun;Song Yang;Wang Xianling;Li Xuying;Wang Chaodong;Li Cunjiang(Department of Neurology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院神经内科,北京100053 [2]贵州中医药大学第二附属医院神经内科

出　　处：《北京医学》2024年第5期374-379,共6页Beijing Medical Journal

摘　　要：目的总结一个LMNB1相关常染色体显性遗传成人型脑白质营养不良(adult-onset autosomal dominant leukodystrophy,ADLD)家系的临床、影像学特点,并进行致病性变异分析。方法选取2023年11月首都医科大学宣武医院确诊为ADLD患者1例,收集先证者及家系其他患者的临床和影像学资料,对先证者进行全外显子组测序分析及LMNB1基因的多重连接探针扩增(multiplex ligation-dependent probe amplification,MLPA)检测,并进行致病性分析和表型匹配分析。结果本例患者(先证者)男,44岁,因“大小便障碍3年,双下肢乏力2年余”就诊,基因检测示LMNB1基因1-11号外显子重复变异,评定为致病性变异,表型与ADLD匹配,先证者(Ⅲ:9)和Ⅲ:6以自主神经功能障碍起病,系ADLD典型表现,Ⅱ:11首发症状为头部震颤,与其他患者不同。结论ADLD患者的LMNB1基因1-11号外显子重复变异,符合常染色体显性遗传方式。成年患者以自主神经功能障碍起病,随后累及小脑、锥体束,MRI示广泛对称的脑白质病变、脊髓萎缩时应考虑ADLD,建议行LMNB1基因检测。Objective To summarize the clinical and imaging features of LMNB1-related adult-onset autosomal dominant leukodystrophy(ADLD),and analyze the pathogenic variation.Methods An ADLD patient diagnosed in Xuanwu Hospital,Capital Medical University in November,2023 was selected,and clinical and imaging data of the proband and other paitents in the family were collected.Whole-exome sequencing(WES)and analysis were completed for the proband and the result was confirmed using multiplex ligation-dependent probe amplification(MLPA)assay,and pathogenicity analysis and phenotype matching analysis were carried out according to the results.Results The patient(proband)was a 44-year-old male,who was treated for defecation disorder for three years and weakness of both lower limbs for more than two years.The genetic test showed duplication of 1-11 coding exons in the LMNB1 gene,which was classified as pathogenic variation,and the phenotype matched with ADLD.The first symptoms of the proband(Ⅲ:9)andⅢ:6 were autonomic dysfunction,which was a typical manifestation of ADLD.However,Ⅱ:11 had head tremor as the first symptom,which was different from other patients.Conclusions A duplication of 1-11 coding exons in the LMNB1 gene is identified,which accords with autosomal dominant inheritance pattern.Adult patients start with autonomic dysfunction,and then involve the cerebellum and pyramidal tract,and when MRI shows extensive symmetrical white matter lesions and spinal cord atrophy,ADLD should be considered,and LMNB1 gene testing is recommended.

关 键 词：LMNB1基因 拷贝数变异 常染色体显性遗传成人型脑白质营养不良 

分 类 号：R742[医药卫生—神经病学与精神病学]