Fox, NC and Kennedy, AM and Harvey, RJ and Lantos, PL and Roques, PK and Collinge, J and Hardy, J and Hutton, M and Stevens, JM and Warrington, EK and Rossor, MN (1997) Clinicopathological features of familial Alzheimer's disease associated with the M139V mutation in the presenilin 1 gene - Pedigree but not mutation specific age at onset provides evidence for a further genetic factor. BRAIN , 120 491 - 501.
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Sixteen affected individuals are described from two families with early onset autosomal dominant familial Alzheimer's disease. A mutation at codon 139 in the presenilin 1 gene on chromosome 14 results in a methionine to valine substitution which cosegregates with the disease in these families. Onset of dementia tvas before the age of 50 years in all individuals. The ages at onset within each family were tightly clustered but were significantly different between the families; this difference could not be accounted for by apolipoprotein E status and suggests the existence of a further genetic factor that modifies age at disease onset. The pattern of cognitive decline was similar in both families: early memory loss (initially selective for verbal memory in some individuals) was followed soon after by loss of arithmetic skills while naming and object perception skills were relatively preserved. A speech production deficit was observed in three members of one family but not in the other. Seizures were common and usually predated by myoclonic jerks by a number of years. Serial MRIs showed progressive cortical atrophy with periventricular white matter change appearing 3-4 years into the disease. PET revealed parieto-temporal hypometabolism in all individuals scanned. The diagnosis of Alzheimer's disease was confirmed with typical histopathology in one individual from each family.
|Title:||Clinicopathological features of familial Alzheimer's disease associated with the M139V mutation in the presenilin 1 gene - Pedigree but not mutation specific age at onset provides evidence for a further genetic factor|
|Keywords:||Alzheimer's disease, familial, chromosome 14, presenilin, early onset, age at onset, PRECURSOR PROTEIN GENE, MISSENSE MUTATION, OF-ONSET, CODON 717, S182 GENE, DEMENTIA, CHROMOSOME-14, HETEROGENEITY, TOMOGRAPHY, MYOCLONUS|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Molecular Neuroscience|
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Neurodegenerative Diseases
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