Rare causes of early-onset dystonia-parkinsonism with cognitive impairment: a de novo PSEN-1 mutation.

Abstract

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.

• Authors: Miryam Carecchio, Marina Picillo, Lorella Valletta, Antonio E Elia, Tobias B Haack, Autilia Cozzolino, Annalisa Vitale, Barbara Garavaglia, Arcangela Iuso, Caterina F Bagella, Sabina Pappatà, Paolo Barone, Holger Prokisch, Luigi Romito, Valeria Tiranti
• Journal: Neurogenetics (Neurogenetics) Vol. 18 Issue 3 Pg. 175-178 (Jul 2017) ISSN: 1364-6753 [Electronic] United States
• PMID: 28664294 (Publication Type: Journal Article)

Chemical References

• PSEN1 protein, human
• Presenilin-1

Topics

• Alzheimer Disease (genetics)
• Brain (metabolism)
• Cognitive Dysfunction (genetics)
• Dystonia (complications, genetics)
• Female
• Humans
• Male
• Mutation (genetics)
• Parkinsonian Disorders (complications, genetics)
• Phenotype
• Presenilin-1 (genetics)