title: Large APP locus duplication in a sporadic case of cerebral haemorrhage.
abstract: We report a 54-year-old man who was admitted to the hospital because of acute neurological symptoms due to a cerebral haemorrhage. Postmortem brain examination revealed a lobar haemorrhage and advanced AD neuropathologic changes associated with severe cerebral amyloid angiopathy. Genetic study evidenced the presence of a large APP locus duplication (APPdup) in the patient and a PSEN1 p.E318G polymorphism in him and his older asymptomatic sibling. The APPdup spanned 14.5 Mb and blocks of segmental duplications were detected in the breakpoints. We propose the replication-based mechanism of Fork Stalling Template Switching (FoSTeS) to explain this APPdup rearrangement.
authors.affiliation: Alzheimer's disease and other Cognitive Disorders Unit, Hospital Clínic-IDIBAPS, C/Villarroel, 170, 08036, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Lladó
authors.forename: Oriol
authors.initials: O
authors.lastname: Grau-Rivera
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Valle
authors.forename: Mircea
authors.initials: M
authors.lastname: Balasa
authors.forename: Víctor
authors.initials: V
authors.lastname: Obach
authors.forename: Sergio
authors.initials: S
authors.lastname: Amaro
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Rey
authors.forename: José L
authors.initials: JL
authors.lastname: Molinuevo
authors.forename: Ellen
authors.initials: E
authors.lastname: Gelpi
authors.forename: Anna
authors.initials: A
authors.lastname: Antonell
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001921:Brain / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics*; D002543:Cerebral Hemorrhage / Q000150:complications*; D020440:Gene Duplication; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1