Pedigree with frontotemporal lobar degeneration--motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9.
Pedigree with frontotemporal lobar degeneration--motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9.
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具有额颞叶变性的谱系 - 运动神经元疾病和焦油DNA结合蛋白-43阳性神经病理学：与9号染色体的遗传联系。
DOI：
10.1186/1471-2377-8-32
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发表时间：
2008-08-29
期刊：
影响因子：
2.6
通讯作者：
Schofield, Peter R.
中科院分区：
文献类型：
--
作者：
Luty, Agnes A.;Kwok, John B. J.;Thompson, Elizabeth M.;Blumbergs, Peter;Brooks, William S.;Loy, Clement T.;Dobson-Stone, Carol;Panegyres, Peter K.;Hecker, Jane;Nicholson, Garth A.;Halliday, Glenda M.;Schofield, Peter R.
额颞叶变性（FTLD）是一种临床、病理和遗传异质性神经退行性疾病，通常伴有神经系统体征，如运动神经元相关的肢体无力、痉挛和瘫痪、帕金森综合征和步态障碍。在神经退行性疾病、额颞叶变性（FTLD）和运动神经元病（MND）的家系中，已经报道了与染色体9 p的连锁。本研究的目的是确定一个多代澳大利亚家庭FTLD-MND的遗传位点。临床回顾和标准神经病理学分析的脑切片从受影响的谱系成员。利用微卫星标记和单核苷酸多态性精细作图进行全基因组扫描。通过直接DNA测序检查候选基因。神经病理学检查发现TDP-43蛋白质的细胞质沉积在三个受影响的人。此外，我们确定了一个家庭成员与临床阿尔茨海默氏病，FTLD-泛素神经病理学。遗传连锁和单倍型分析，确定了染色体9 p21上标记D9 S169和D9 S1845之间的关键区域。筛选该区域内的所有候选基因没有发现与疾病单倍型共分离的任何新的遗传改变，这表明携带减数分裂重组的一个个体可能代表表型。重新分析的连锁数据，使用新的影响状态显示，最大的两个点的LOD得分为3.24和3.41标记D9 S1817的多点LOD得分。这提供了来自单个FTLD-MND谱系的最高报告LOD评分。我们报告的最小病变区域的增加应该告知其他研究人员，9号染色体位点可能比已发表的重组边界预测的更端粒。此外，临床阿尔茨海默病的家庭成员的存在，谁共享疾病单倍型，突出了晚发性AD患者在其他连锁家系可能被错误分类为散发性痴呆病例的可能性。
Frontotemporal lobar degeneration (FTLD) represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND). The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease haplotype, highlights the possibility that late-onset AD patients in the other linked pedigrees may be mis-classified as sporadic dementia cases.
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影响因子：
6
作者：
Cairns, Nigel J.;Neumann, Manuela;Mackenzie, Ian R. A.
通讯作者：
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影响因子：
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作者：
Ratnavalli, E;Brayne, C;Hodges, JR
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Hodges, JR
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作者：
Badenhop, RF;Moses, MJ;Schofield, PR
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Schofield, PR
影响因子：
120.7
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作者：
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