Heutink P, Stevens M, Rizzu P, Bakker E, Kros J M, Tibben A, Niermeijer M F, van Duijn C M, Oostra B A, van Swieten J C
Department of Clincial Genetics, Erasmus University Rotterdam, The Netherlands.
Ann Neurol. 1997 Feb;41(2):150-9. doi: 10.1002/ana.410410205.
Hereditary frontotemporal dementia (HFTD) is a rare autosomal dominant form of presenile dementia characterized by behavioral changes and reduced speech. Three multigeneration kindreds with this condition, in the Netherlands, were investigated for clinicopathological comparison and linkage analysis. Frontotemporal atrophy on computed tomographic scanning and/or magnetic resonance imaging was usually present. Single-photon emission computed tomography (SPECT) showed frontal hypoperfusion in the early phase of the disease. Brain tissue showed moderate to severe atrophy of frontal and temporal cortex with neuronal loss, gliosis, and spongiosis. Pick bodies were lacking in all cases of the 3 families. The mean age of onset varied significantly between families. We report here evidence for linkage to chromosome 17q21-q22 with a maximum lod score of 4.70 at theta = 0.05 with the marker D17S932. Recombination analysis positions the gene for HFTD in a region of approximately 5 cM between markers D17S946 and D17S791. Three other neurodegenerative disorders with a strong clinical and pathological resemblance have recently been mapped to the same chromosomal region, suggesting that a group of clinically related neurodegenerative disorders may originate from mutations in the same gene.
遗传性额颞叶痴呆（HFTD）是一种罕见的常染色体显性遗传的早老性痴呆，其特征为行为改变和言语减少。对荷兰的三个患有此病的多代家族进行了临床病理比较和连锁分析。计算机断层扫描和/或磁共振成像通常显示额颞叶萎缩。单光子发射计算机断层扫描（SPECT）显示在疾病早期额叶灌注不足。脑组织显示额颞叶皮质中度至重度萎缩，伴有神经元丧失、胶质增生和海绵状变性。在这三个家族的所有病例中均未发现Pick小体。各家族之间的平均发病年龄差异显著。我们在此报告与17号染色体q21 - q22区域连锁的证据，在θ = 0.05时，与标记D17S932的最大对数优势得分为4.70。重组分析将HFTD基因定位在标记D17S946和D17S791之间约5厘摩的区域。最近，另外三种在临床和病理上有强烈相似性的神经退行性疾病也被定位到同一染色体区域，这表明一组临床相关的神经退行性疾病可能起源于同一基因的突变。
