title: A presenilin 1 mutation (Arg278Ser) associated with early onset Alzheimer's disease and spastic paraparesis.
abstract: Early onset familial Alzheimer's disease (EOFAD) has been associated with mutations in three genes, of which presenilin 1 (PSEN1) mutations are the most frequent. Several families with an association of progressive dementia and spastic paraplegia caused by PSEN1 mutations have been described. Here we described a novel PSEN1 mutation that was associated with dementia and spastic paraplegia in a family with 5 affected individuals in three generations. The proband was a 44-year-old woman who presented with 5 years history of progressive difficulties in walking, cognition and visuospatial impairment. Her maternal grandmother, mother and two maternal aunts also had similar neurological presentation. Molecular genetic analysis showed a missense mutation predicted to substitute an arginine residue for a serine residue at position 278 in the PSEN1 polypeptide (Arg278Ser). The novel PSEN1 mutation identified in this patient adds to the diverse list of existing mutations causing EOFAD associated with spastic paraparesis.
authors.affiliation: University of Nottingham Division of Clinical Neurosciences, University Hospital, Queen's Medical Centre, Nottingham, UK.
authors.forename: Ashok
authors.initials: A
authors.lastname: Raman
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.forename: Mohnish
authors.initials: M
authors.lastname: Suri
authors.forename: Monica
authors.initials: M
authors.lastname: Hewitt
authors.forename: Cris S
authors.initials: CS
authors.lastname: Constantinescu
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Phillips
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D019943:Amino Acid Substitution / Q000235:genetics; D001284:Atrophy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D020336:Paraparesis, Spastic / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: D053764:Presenilin-1