Memory Clinic, Center for Geriatrics and Gerontology Freiburg, University Hospital Freiburg, Lehener Str. 88, 79106 Freiburg, Germany.
J Neurol. 2009 Dec;256(12):2043-51. doi: 10.1007/s00415-009-5248-6. Epub 2009 Jul 19.
Mutations of the progranulin gene lead to progranulin haploinsufficiency and to frontotemporal lobar degeneration (FTD) with TDP-43 positive inclusions. It is assumed that unknown genetic, epigenetic and environmental factors are responsible for the observed marked degree of phenotypic variability among mutation carriers. This is the first published series of German FTD cases screened for progranulin mutations. Mean age at onset was 62 years, 19 patients (24%) had a positive family history of dementia, and 11 patients (14%) had a positive family history for probable FTD. Data on FTD subtypes are presented. Two mutations were identified (3%), one of which has been described previously. Clinically, both patients showed the frontal-behavioural variant type of FTD. Remarkably, a sibling of one case presented with progressive nonfluent aphasia, clinically distinct from the brother. We also performed quantitative PCR analyses to detect potential whole progranulin gene and exon deletions. Here, results were negative.
颗粒蛋白前体基因的突变导致颗粒蛋白单倍体不足，并伴有 TDP-43 阳性包涵体的额颞叶变性（FTD）。据推测，未知的遗传、表观遗传和环境因素是导致突变携带者表现出明显程度的表型变异性的原因。这是第一个对德国 FTD 病例进行颗粒蛋白突变筛查的系列研究。发病年龄的平均值为 62 岁，19 名患者（24%）有痴呆的阳性家族史，11 名患者（14%）有 FTD 的阳性家族史。还介绍了 FTD 亚型的数据。鉴定出两种突变（3%），其中一种以前已有描述。临床上，两名患者均表现为额颞叶行为变异型 FTD。值得注意的是，一例患者的一位同胞表现出进行性非流利性失语症，与兄弟的临床表现不同。我们还进行了定量 PCR 分析，以检测潜在的整个颗粒蛋白基因和外显子缺失。结果为阴性。
