Institute for Neurosciences, St. Luke's Medical Center, Quezon City, Philippines,
Institute for Neurosciences, St. Luke's Medical Center, Quezon City, Philippines.
Dement Geriatr Cogn Disord. 2020;49(6):557-564. doi: 10.1159/000510106. Epub 2021 Jan 22.
Compared to Western populations, familial frontotemporal lobar degeneration (FTLD) is rare among Asians. Progranulin (GRN) gene mutation, which is a major cause of FTLD, is likewise rare. We present a family with FTLD from the Philippines with an autosomal dominant pattern of inheritance and GRN mutation and briefly review reports of GRN mutations in Asia.
The proband is 66 years old with progressive nonfluent aphasia (PNFA)-corticobasal syndrome . We assessed 3 generations of her pedigree and found 11 affected relatives with heterogenous phenotypes, usually behavioral variant frontotemporal dementia (FTD) and PNFA. Neuroimaging showed atrophy and hypometabolism consistent with FTD syndromes. White matter hyperintensities were seen in affected members even in the absence of vascular risk factors. A GRN mutation R110X was found in 6 members, 3 with symptoms and 3 were asymptomatic. Plasma GRN was low (<112 ng/mL) in all mutation carriers. No mutations were found in microtubule-associated protein tau, APP, PSEN1, and PSEN2 genes, and all were APOE3.
This is the first Filipino family with autosomal dominant FTD documented with GRN mutation. Identifying families and cohorts would contribute to therapeutic developments in an area with FTD-GRN.
与西方人群相比，家族性额颞叶变性（FTLD）在亚洲人群中较为少见。颗粒蛋白前体（GRN）基因突变是 FTLD 的主要病因之一，在亚洲也较为少见。我们报告了一个来自菲律宾的 FTLD 家系，呈常染色体显性遗传模式，伴有 GRN 突变，并简要回顾了亚洲的 GRN 突变报告。
先证者 66 岁，表现为进行性非流利性失语（PNFA）-皮质基底节综合征。我们评估了她的 3 代家系，发现 11 名受累亲属具有异质性表型，通常为行为变异额颞痴呆（FTD）和 PNFA。神经影像学显示与 FTD 综合征一致的萎缩和低代谢。即使没有血管危险因素，受累成员也可见脑白质高信号。在 6 名成员中发现了 GRN 突变 R110X，其中 3 名有症状，3 名无症状。所有突变携带者的血浆 GRN 均较低（<112ng/ml）。微管相关蛋白 tau、APP、PSEN1 和 PSEN2 基因未发现突变，所有均为 APOE3。
这是首例记录在案的菲律宾常染色体显性 FTD 伴 GRN 突变的家系。鉴定家系和队列将有助于 FTD-GRN 领域的治疗发展。
