Cognitive Function Clinic, Walton Centre for Neurology and Neurosurgery, Liverpool, United Kingdom.
J Neurol Sci. 2012 May 15;316(1-2):189-90. doi: 10.1016/j.jns.2012.01.005. Epub 2012 Jan 26.
A patient with a progressive aphasia syndrome underwent progranulin gene (GRN) testing in light of a family history of early-onset dementia in two of her brothers, one of whom had been previously examined and had the phenotype of frontal variant frontotemporal dementia. The proband was found to have the p.Glu498fs mutation. This is only the second English family, and the fifth family overall, to be described with this GRN mutation. There was marked intrafamilial phenotypic heterogeneity with respect to age at onset and clinical presentation. The mechanisms underpinning this heterogeneity, as seen with other GRN mutations, are currently unknown. Since all GRN mutations lead to progranulin haploinsufficiency, other modifying factors, possibly genetic, are implicated.
一位进行性失语综合征患者，鉴于其两名兄弟均有早发性痴呆家族史，其中一名曾被检查出额颞叶痴呆变异型表型，故对其进行颗粒体蛋白基因（GRN）检测。该先证者被发现存在 p.Glu498fs 突变。这是第二个被描述的具有该 GRN 突变的英语家族，也是第五个具有该突变的家族。在发病年龄和临床表现方面，家族内存在明显的表型异质性。与其他 GRN 突变一样，目前尚不清楚导致这种异质性的机制。由于所有 GRN 突变均导致颗粒体蛋白单倍体不足，因此可能涉及其他修饰因子，可能是遗传因素。
