Synofzik M, Bauer P, Schöls L
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
J Neurol Neurosurg Psychiatry. 2009 Mar;80(3):345-6. doi: 10.1136/jnnp.2008.149922.
Hereditary prion disease is a fatal genetic disorder of autosomal dominant inheritance. Recent phenotype-genotype correlation studies revealed a considerable clinical and pathological overlap for patients with the D178N mutation, suggesting a continuous spectrum between fatal familial insomnia and Creutzfeldt-Jakob Disease phenotype. This report adds further evidence to this thesis from a large German prion pedigree with D178N mutation in the PRNP-gene. This pedigree shows an extensive variability in (1) age of disease onset, ranging from 19 to 72 years and including an asymptomatic 73-year-old gene carrier and (2) disease phenotype, including a Gerstmann-Straussler-Scheinker phenotype. These findings have substantial importance for genetic counselling of persons at risk.
遗传性朊病毒病是一种常染色体显性遗传的致命性基因疾病。最近的表型-基因型相关性研究显示，携带D178N突变的患者在临床和病理方面存在相当大的重叠，这表明致死性家族性失眠症和克雅氏病表型之间存在连续谱。本报告从一个在PRNP基因中存在D178N突变的大型德国朊病毒家系为这一论点提供了进一步的证据。这个家系在以下两方面表现出广泛的变异性：（1）发病年龄，范围从19岁到72岁，包括一名73岁无症状的基因携带者；（2）疾病表型，包括格斯特曼-施特劳斯勒-谢inker表型。这些发现对于有患病风险人群的遗传咨询具有重要意义。
