title: A novel mutation in the PSEN1 gene (L286P) associated with familial early-onset dementia of Alzheimer type and lobar haematomas.
abstract: The aim of this study was to describe a novel mutation in exon 8 of the presenilin gene (L286P) associated with early-onset autosomal dominant Alzheimer's disease (AD) and lobar haematomas. The proband was a woman who developed cognitive decline with predominant memory loss at the age of 35 years. The patient died at the age of 54 years and the neuropathological examination confirmed the diagnosis of AD. Three of her four siblings, one parent and one sibling of her parent had suffered from cognitive decline at ages between 35 and 42 years. Three of them also presented lobar haematomas. The neuropathological examination, available in one of them, disclosed the presence of severe amyloid angiopathy as the cause of the haematoma. The study of PSEN1 gene with single strand conformation polymorphism technique failed to show abnormalities suggestive of mutations. Direct sequencing disclosed the presence of a missense mutation in codon 286 (L286P) in the proband and her already affected descendent, which was absent in the healthy sibling. L286P is a novel mutation in PSEN1 that causes familial early-onset AD and brain haematomas related to amyloid angiopathy.
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Barcelona, Spain. rsanchez@clinic.ub.es
authors.forename: R
authors.initials: R
authors.lastname: Sánchez-Valle
authors.forename: A
authors.initials: A
authors.lastname: Lladó
authors.forename: M
authors.initials: M
authors.lastname: Ezquerra
authors.forename: M J
authors.initials: MJ
authors.lastname: Rey
authors.forename: L
authors.initials: L
authors.lastname: Rami
authors.forename: J L
authors.initials: JL
authors.lastname: Molinuevo
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1