Carecchio Miryam, Picillo Marina, Valletta Lorella, Elia Antonio E, Haack Tobias B, Cozzolino Autilia, Vitale Annalisa, Garavaglia Barbara, Iuso Arcangela, Bagella Caterina F, Pappatà Sabina, Barone Paolo, Prokisch Holger, Romito Luigi, Tiranti Valeria
Molecular Neurogenetics Unit, IRCCS Foundation C. Besta Neurological Institute, Via L. Temolo n. 4, 20126, Milan, Italy.
Department of Child Neurology, IRCCS Foundation C. Besta Neurological Institute, Via Celoria 11, 20133, Milan, Italy.
Neurogenetics. 2017 Jul;18(3):175-178. doi: 10.1007/s10048-017-0518-4. Epub 2017 Jun 29.
Mutations in PSEN1 are responsible for familial Alzheimer's disease (FAD) inherited as autosomal dominant trait, but also de novo mutations have been rarely reported in sporadic early-onset dementia cases. Parkinsonism in FAD has been mainly described in advanced disease stages. We characterized a patient presenting with early-onset dystonia-parkinsonism later complicated by dementia and myoclonus. Brain MRI showed signs of iron accumulation in the basal ganglia mimicking neurodegeneration with brain iron accumulation (NBIA) as well as fronto-temporal atrophy. Whole exome sequencing revealed a novel PSEN1 mutation and segregation within the family demonstrated the mutation arose de novo.We suggest considering PSEN1 mutations in cases of dystonia-parkinsonism with positive DAT-Scan, later complicated by progressive cognitive decline and cortical myoclonus even without a dominant family history.
PSEN1基因的突变是导致常染色体显性遗传的家族性阿尔茨海默病（FAD）的原因，但在散发性早发性痴呆病例中也很少有新发突变的报道。FAD中的帕金森综合征主要出现在疾病晚期。我们对一名患者进行了特征描述，该患者表现为早发性肌张力障碍 - 帕金森综合征，随后并发痴呆和肌阵挛。脑部MRI显示基底神经节有铁沉积迹象，类似脑铁沉积性神经变性（NBIA）以及额颞叶萎缩。全外显子组测序发现了一种新的PSEN1突变，家族内的遗传分析表明该突变是新发的。我们建议，对于DAT扫描呈阳性、随后并发进行性认知衰退和皮质肌阵挛的肌张力障碍 - 帕金森综合征病例，即使没有显性家族史，也应考虑PSEN1突变的可能性。
