Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
J Alzheimers Dis. 2023;93(1):225-234. doi: 10.3233/JAD-230052.
Progranulin (GRN) mutations in frontotemporal dementia (FTD) have been less frequently reported in China than in Western countries.
This study reports a novel GRN mutation and summarizes the genetic and clinical features of patients with GRN mutations in China.
Comprehensive clinical, genetic, and neuroimaging examinations were conducted on a 58-year-old female patient diagnosed with semantic variant primary progressive aphasia. A literature review was also conducted and clinical and genetic features of patients with GRN mutations in China were summarized.
Neuroimaging revealed marked lateral atrophy and hypometabolism in the left frontal, temporal, and parietal lobes. The patient was negative for pathologic amyloid and tau deposition by positron emission tomography. A novel heterozygous 45-bp deletion (c.1414-14_1444delCCCTTCCCCGCCAGGCTGTGTGCTGCGAGGATCGCCAGCACTGCT) was detected by whole-exome sequencing of the patient's genomic DNA. Nonsense-mediated mRNA decay was presumed to be involved in the degradation of the mutant gene transcript. The mutation was deemed pathogenic according to American College of Medical Genetics and Genomics criteria. The patient had a reduced plasma GRN level. In the literature, there were reports of 13 Chinese patients - mostly female - with GRN mutations; the prevalence was 1.2% -2.6% and patients mostly had early disease onset.
Our findings expand the mutation profile of GRN in China, which can aid the diagnosis and treatment of FTD.
在中国，与西方国家相比，颗粒体蛋白前体（GRN）突变在额颞叶痴呆（FTD）中的报道较少。
本研究报告了一种新的 GRN 突变，并总结了中国 GRN 突变患者的遗传和临床特征。
对一名 58 岁女性语义性进行性失语症患者进行了全面的临床、遗传和神经影像学检查。还进行了文献复习，总结了中国 GRN 突变患者的临床和遗传特征。
神经影像学显示左侧额、颞、顶叶明显的外侧萎缩和低代谢。患者正电子发射断层扫描（PET）检查结果为病理性淀粉样蛋白和 tau 沉积阴性。通过对患者基因组 DNA 的全外显子组测序发现了一个新的杂合 45-bp 缺失（c.1414-14_1444delCCCTTCCCCGCCAGGCTGTGTGCTGCGAGGATCGCCAGCACTGCT）。推测无义介导的 mRNA 衰减参与了突变基因转录本的降解。根据美国医学遗传学与基因组学学院（ACMG）标准，该突变被认为是致病性的。患者的血浆 GRN 水平降低。文献中有 13 例中国患者（多为女性）携带 GRN 突变的报告，患病率为 1.2%至 2.6%，患者多为早发型。
我们的发现扩展了中国 GRN 的突变谱，有助于 FTD 的诊断和治疗。
