Department of Neurology, Maison Blanche Hospital, Reims University Hospital, Reims, France.
J Alzheimers Dis. 2013;37(4):769-76. doi: 10.3233/JAD-130413.
Frontotemporal lobe degeneration includes a large spectrum of neurodegenerative disorders. Patients with frontotemporal dementia with parkinsonism linked to chromosome 17 exhibit heterogeneity in both clinical and neuropathological features. Here, we report the case of a young patient with a G389R mutation. This teenager girl was 17 years old when she progressively developed severe behavioral disturbances. First, she was considered to be suffering from atypical depression. After 2 years, she was referred to the department of neurology. By this time, the patient exhibited typical frontotemporal dementia with mild extrapyramidal disorders. The main behavioral features included apathy and reduced speech output. MRI and SPECT showed a frontotemporal atrophy and hypofixation, respectively. She died 7 years after onset. Three relatives on her father side had also died after early onset dementia. Genetic testing revealed a heterozygous guanine to cytosine mutation at the first base of codon 389 (Exon 13) of MAPT, the tau gene, resulting in a glycine to arginine substitution, in the patient and her non-affected father. Postmortem neuropathological and biochemical data indicate a Pick-like tau pathology but with phosphoserine 262-positive immunoreactivity. This case is remarkable because of the extremely early onset of the disease.
额颞叶变性包括一大类神经退行性疾病。具有帕金森病特征的额颞叶痴呆与 17 号染色体相关的患者在临床和神经病理学特征上存在异质性。在这里，我们报告了一例携带 G389R 突变的年轻患者。这名少女在 17 岁时逐渐出现严重的行为障碍。起初，她被认为患有非典型抑郁症。2 年后，她被转至神经内科。此时，患者表现出典型的额颞叶痴呆伴轻度锥体外系障碍。主要的行为特征包括冷漠和言语输出减少。MRI 和 SPECT 分别显示额颞叶萎缩和低固定。发病后 7 年，她去世了。她父亲一方的 3 位亲属也在早期发病痴呆后去世。基因检测显示，患者及其未患病的父亲在 MAPT（微管相关蛋白 tau 基因）第 389 密码子的第一个碱基（外显子 13）处存在鸟嘌呤到胞嘧啶的杂合突变，导致甘氨酸到精氨酸取代。尸检神经病理学和生物化学数据表明存在类 Pick tau 病理学，但磷酸丝氨酸 262 阳性免疫反应。这个病例很显著，因为疾病的发病年龄极早。
