Abstract：
BACKGROUND: Mutations in the progranulin gene on chromosome 17(GRN) is considered as one of most common causes of frontotemporal lobe degeneration. However, the phenotype and genotype correlation of GRN varies among different cohorts and ethnicities. In Chinese people, the genotype of GRN has not been fully elucidated.
METHODS: 1945 patients with dementia at Peking Union Medical College Hospital underwent next-generation sequencing (NGS) analysis. GRN variations classified as likely pathogenic and of uncertain significance were identified. Demographic information, clinical presentations, and neuroimaging were collected. The clinical, neuropsychological and neuroimaging characters were investigated.
RESULTS: Three patients with four likely pathogenic mutation: p.P50fs & p.W49_P50delinsX, p.P439fs, p.R110X, and thirteen patients with uncertain significance mutations were enrolled. Cognitive dysfunction, behavior, and personality changes as well as aphasia were the most common presentations. Asymmetrical atrophy of the frontal lobe and temporal lobe appeared in 64% GRN mutation carriers. Parietal lobe dysfunction or parietal lobe atrophy existed in all patients. White matter lesions existed in 79% patients. The majority of clinical phenotype was frontotemporal lobe degeneration, though cerebral vascular lesions were obvious in some of them especially among old onset patients. The proportion of ApoE e4 carriers were higher in old onset patients than those in young onset ones.
CONCLUSIONS: GRN mutation is rare in Chinese dementia patients. The phenotype and genotype correlation is specific and overlaps.
METHODS: 1945 patients with dementia at Peking Union Medical College Hospital underwent next-generation sequencing (NGS) analysis. GRN variations classified as likely pathogenic and of uncertain significance were identified. Demographic information, clinical presentations, and neuroimaging were collected. The clinical, neuropsychological and neuroimaging characters were investigated.
RESULTS: Three patients with four likely pathogenic mutation: p.P50fs & p.W49_P50delinsX, p.P439fs, p.R110X, and thirteen patients with uncertain significance mutations were enrolled. Cognitive dysfunction, behavior, and personality changes as well as aphasia were the most common presentations. Asymmetrical atrophy of the frontal lobe and temporal lobe appeared in 64% GRN mutation carriers. Parietal lobe dysfunction or parietal lobe atrophy existed in all patients. White matter lesions existed in 79% patients. The majority of clinical phenotype was frontotemporal lobe degeneration, though cerebral vascular lesions were obvious in some of them especially among old onset patients. The proportion of ApoE e4 carriers were higher in old onset patients than those in young onset ones.
CONCLUSIONS: GRN mutation is rare in Chinese dementia patients. The phenotype and genotype correlation is specific and overlaps.
摘要：
背景：17号染色体（GRN）上的颗粒蛋白前体基因突变被认为是额颞叶变性的最常见原因之一。然而,GRN的表型和基因型相关性在不同队列和种族之间存在差异.在中国人，GRN的基因型尚未完全阐明。
方法：1945例北京协和医院痴呆患者进行了下一代测序（NGS）分析。鉴定了被分类为可能致病且意义不确定的GRN变异。人口统计信息,临床表现,并收集神经影像学。临床，研究了神经心理学和神经影像学特征。
结果：三例患者有四种可能的致病突变：p.P50fs和p.W49_P50delinsX，p.P439fs,p.R110X,纳入了13例具有不确定意义突变的患者。认知功能障碍,行为，人格变化和失语症是最常见的表现。64％的GRN突变携带者出现了额叶和颞叶的不对称萎缩。所有患者均存在顶叶功能障碍或顶叶萎缩。79%的患者存在白质病变。大多数临床表型是额颞叶变性，尽管其中一些脑血管病变明显，尤其是老年患者。老年患者ApoEe4携带者的比例高于年轻患者。
结论：GRN突变在中国痴呆患者中罕见。表型和基因型相关性是特异性的和重叠的。
方法：1945例北京协和医院痴呆患者进行了下一代测序（NGS）分析。鉴定了被分类为可能致病且意义不确定的GRN变异。人口统计信息,临床表现,并收集神经影像学。临床，研究了神经心理学和神经影像学特征。
结果：三例患者有四种可能的致病突变：p.P50fs和p.W49_P50delinsX，p.P439fs,p.R110X,纳入了13例具有不确定意义突变的患者。认知功能障碍,行为，人格变化和失语症是最常见的表现。64％的GRN突变携带者出现了额叶和颞叶的不对称萎缩。所有患者均存在顶叶功能障碍或顶叶萎缩。79%的患者存在白质病变。大多数临床表型是额颞叶变性，尽管其中一些脑血管病变明显，尤其是老年患者。老年患者ApoEe4携带者的比例高于年轻患者。
结论：GRN突变在中国痴呆患者中罕见。表型和基因型相关性是特异性的和重叠的。
