A novel deletion in progranulin gene is associated with FTDP-17 and CBS
A novel deletion in progranulin gene is associated with FTDP-17 and CBS
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DOI：
10.1016/j.neurobiolaging.2006.10.028
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发表时间：
2008-03-01
影响因子：
4.2
通讯作者：
Ghidoni, Roberta
中科院分区：
文献类型：
--
作者：
Benussi, Luisa;Binetti, Giuliano;Ghidoni, Roberta
在过去的十年中，家族性额颞叶痴呆（FFTD）已经成为一种独特的临床疾病实体，其特征是临床和遗传异质性。在这里，我们提供了两个意大利家系FFTD的广泛临床和遗传特征（FAM047: 5例患者，5例未受影响；FAM071: 4例患者，11例未受影响）。遗传分析显示，D17S791/D17S951与17号染色体存在决定性连锁（LOD评分：4.173），并确定了包含MAPT和PGRN基因的候选区域。重组分析为FAM047和FAM071分配了两种不同的疾病单倍型。在属于这两个家族的受影响受试者中，我们在PGRN基因（Leu271LeufsX10）的第7外显子中发现了一个新的4bp缺失突变，该突变与FTDP-17到皮质基底综合征的可变临床表现相关。与年龄相关的外显率与性别有关。MAPT和PGRN基因的突变都与高度可变的临床表型相关。尽管编码蛋白的生物学功能存在深刻差异，但不可能定义一种临床表型来区分由MAPT和PGRN基因突变引起的疾病。(C) 2006爱思唯尔公司版权所有。
In the last decade familial frontotemporal dementia (FFTD) has emerged as a distinct clinical disease entity characterized by clinical and genetic heterogeneity.Here, we provide an extensive clinical and genetic characterization of two Italian pedigrees presenting with FFTD (FAM047: 5 patients, 5 unaffected; FAM071: 4 patients, 11 unaffected). Genetic analysis showed a conclusive linkage (LOD score for D17S791/D17S951: 4.173) to chromosome 17 and defined a candidate region containing MAPT and PGRN genes. Recombination analysis assigned two different disease haplotypes to FAM047 and FAM071. In affected subjects belonging to both families, we identified a novel 4 bp deletion mutation in exon 7 of PGRN gene (Leu271LeufsX10) associated with a variable clinical presentation ranging from FTDP-17 to corticobasal syndrome. The age-related penetrance was gender dependent.Both mutations in MAPT and PGRN genes are associated with highly variable clinical phenotypes. Despite the profound differences in the biological functions of the encoded proteins, it is not possible to define a clinical phenotype distinguishing the disease caused by mutations in MAPT and PGRN genes. (C) 2006 Elsevier Inc. All rights reserved.