A novel frameshift GRN mutation results in frontotemporal lobar degeneration with a distinct clinical phenotype in two siblings: case report and literature review

被引:11
作者
Hosaka, Takashi [1 ]
Ishii, Kazuhiro [1 ]
Miura, Takeshi [2 ,3 ]
Mezaki, Naomi [2 ,3 ]
Kasuga, Kensaku [2 ]
Ikeuchi, Takeshi [2 ]
Tamaoka, Akira [1 ]
机构
[1] Univ Tsukuba, Div Clin Med, Dept Neurol, Fac Med, 1-1-1 Tennoudai, Tsukuba, Ibaraki 3058575, Japan
[2] Niigata Univ, Brain Res Inst, Dept Mol Genet, 1-757 Asahimachi, Niigata 9518585, Japan
[3] Niigata Univ, Brain Res Inst, Dept Neurol, 1-757 Asahimachi, Niigata 9518585, Japan
来源
BMC NEUROLOGY | 2017年 / 17卷
关键词
Progranulin; Primary progressive aphasia; Corticobasal syndrome; Frontotemporal lobar degeneration; Phenotypic heterogeneity; Case report; PROGRANULIN MUTATION; CORTICOBASAL SYNDROME; EXPRESSION; GENE; DEMENTIA; DISEASE; FTLD; TAU; CBS;
D O I
10.1186/s12883-017-0959-2
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Progranulin gene (GRN) mutations are major causes of frontotemporal lobar degeneration. To date, 68 pathogenic GRN mutations have been identified. However, very few of these mutations have been reported in Asians. Moreover, some GRN mutations manifest with familial phenotypic heterogeneity. Here, we present a novel GRN mutation resulting in frontotemporal lobar degeneration with a distinct clinical phenotype, and we review reports of GRN mutations associated with familial phenotypic heterogeneity. Case presentation: We describe the case of a 74-year-old woman with left frontotemporal lobe atrophy who presented with progressive anarthria and non-fluent aphasia. Her brother had been diagnosed with corticobasal syndrome (CBS) with right-hand limb-kinetic apraxia, aphasia, and a similar pattern of brain atrophy. Laboratory blood examinations did not reveal abnormalities that could have caused cognitive dysfunction. In the cerebrospinal fluid, cell counts and protein concentrations were within normal ranges, and concentrations of tau protein and phosphorylated tau protein were also normal. Since similar familial cases due to mutation of GRN and microtubule-associated protein tau gene (MAPT) were reported, we performed genetic analysis. No pathological mutations of MAPT were identified, but we identified a novel GRN frameshift mutation (c. 1118_1119delCCinsG:p.Pro373ArgX37) that resulted in progranulin haploinsufficiency. Conclusion: This is the first report of a GRN mutation associated with familial phenotypic heterogeneity in Japan. Literature review of GRN mutations associated with familial phenotypic heterogeneity revealed no tendency of mutation sites. The role of progranulin has been reported in this and other neurodegenerative diseases, and the analysis of GRN mutations may lead to the discovery of a new therapeutic target.
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页数:6
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