TREM2新纯合突变致早发痴呆(附一家系报告及文献复习)

A Homozygous Mutation in TREM2 Found in An Early-onset Dementia Patient

目的报道1例髓样细胞触发受体2(TREM2)基因纯合突变致早发、常染色体隐性遗传性痴呆病例。方法收集1例以认知损害患者的主要临床表现、影像学及家系资料,采用基因测序检测TREM2基因多态性,并结合文献复习进行分析讨论。结果患者为40岁汉族女性,其家系调查系一近亲婚配家系,患者临床表现为进行性认知损害、个性改变、行为异常,影像学检查显示骨骼轻微累及。基因测序提示TREM2外显子区域一处纯合突变(c.391+1G>A)。Minigene报告基因分析:此突变干扰基因剪接,导致氨基酸剪切改变。TREM2基因突变与散发性行为变异型额颞叶痴呆及阿尔茨海默病有关。TREM2纯合突变可导致Nasu-Hakola病,临床表现为早发、常染色体隐性遗传性痴呆,伴随早期多发骨囊肿及病理性骨折;亦可导致无骨质累及的额颞叶痴呆。结论早发、家族性中国汉族痴呆患者,遗传学筛查应纳入TREM2基因检测。

Aim To report a case of early-onset autosomal recessive dementia caused by homozygous mutation of the myeloid cell trigger receptor 2(TREM2)gene.Methods The clinical,imaging and pedigree data of a patient with cognitive impairment as the main clinical manifestation were collected,and the polymorphism of TREM2 gene was detected by gene sequencing and the related literature was reviewed.Results Herein,we report a Chinese Han consanguineous family carrying a novel TREM2 mutation,presenting with early-onset dementia similar to behavioral variant frontotemporal dementia(bvFTD)with mild radiological bone involvement.The gene sequencing indicated a homozygous mutation in the exon region of TREM2(c.391+1 G>A).Minigene reporter assay showed the variant disturbed splicing by preservation of intron 2 in transcription.In our investigation,the clinical and genetic spectra of Chinese early-onset dementia patients were expanded.Conclusion TREM2 mutations should be screened in familial and Chinese early-onset dementia patients.