髓样细胞触发受体2基因突变致早发型痴呆一家系分析

Analysis of a family with early-onset dementia caused by a new mutation in the triggerring receptor expressing on myeloid cells 2 gene

目的分析髓样细胞触发受体2基因新突变致早发型痴呆一家系的临床表型、影像学特点及遗传学特征。方法对1例2019年9月26日就诊于郑州大学人民医院,表现为额颞叶痴呆样症候群的早发型痴呆患者及其家系成员进行临床资料和影像学特征采集,并对先证者进行人类全外显子测序,对家系成员进行一代验证。结果先证者为49岁女性,临床表现为性格改变、精神行为异常、记忆力下降、共济失调、癫痫发作。基因检测发现先证者髓样细胞触发受体2基因第154位密码子发生p.R52C纯合突变,家系中4名成员为杂合携带者,1名有类似临床表现者已故,无法检测。先证者头颅磁共振成像显示双侧额颞叶萎缩、双侧白质高信号、胼胝体变薄,双手、足部平片未发现有骨囊变改变。结论患者表型为额颞叶痴呆样痴呆、癫痫,不伴有骨囊变,基因检测显示髓样细胞触发受体2基因纯合突变。该突变很可能为致病突变。对早发型痴呆,尤其当伴有癫痫发作、共济失调不典型表现时,应进行髓样细胞触发受体2基因检测。

Objective To analyze the clinical phenotype,imaging characteristics and genetic characteristics of a family of early-onset dementia caused by a new mutation in the triggerring receptor expressing on myeloid cells 2 gene(TREM2).Methods Clinical data were collected from a patient with early-onset dementia.Then whole exome sequencing was performed for the proband,followed by Sanger sequencing for the family members.Results The clinical manifestations of the proband(a 49-year-old female)was personality changes,mental and behavioral abnormalities,memory loss,ataxia,and seizures.Whole-exon sequencing revealed a novel homozygous mutation in exon 2 of TREM2,namely c.154C>T(p.R52C)heterozygosity in four family members,and one patient with similar clinical manifestations was deceased.The proband′s brain magnetic resonance imaging showed bilateral frontotemporal atrophy,bilateral white matter hyperintensity,thin corpus callosum.No bone cysts of the hands and feet were found by digital radiographic imaging.Conclusions A homozygous mutation in TREM2 gene was detected in a patient with frontotemporal dementia-like dementia,epilepsy,but without bone cysts.This mutation is probably pathogenic.This research highlights the importance of TREM2 gene mutation screening in early-onset dementia,especially in those with atypical presentations.