Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.38794T>G
Genomic Mutation Name (NT1): g.55399T>G
dbSNP ID: rs63750265
Genomic Region: Exon 6
Mutation Type: Point, Missense
Codon Change: CTT to CGT
This mutation is associated with early onset Alzheimer’s disease in a family of Spanish origin. The reported pedigree contains six affected individuals over three generations. In this family, symptoms became apparent between the ages of 32 and 44. The proband began to experience memory decline at age 32. A neurological exam also showed a grasping reflex and bradykinesia. The proband’s mother was also affected, but her age of onset is unknown. His maternal aunt experienced memory loss at age 44, along with irritability and depression. She also developed aphasia and akinetic movements. The mutation was found to segregate with disease; it was present in the proband but absent in two healthy family members aged 37 and 60. The L166R mutation was also detected in two healthy individuals, who, at age 25 and 28, were below the average age of onset in this family (Ezquerra et al., 2000). This family was included in a later mutation-prevalence study conducted in Spain (Lleó et al., 2002).
Unknown. MRI of the proband showed cortical atrophy and PET showed parietal hypoperfusion (Ezquerra et al., 2000).
- Ezquerra M, Carnero C, Blesa R, Oliva R. A novel presenilin 1 mutation (Leu166Arg) associated with early-onset Alzheimer disease. Arch Neurol. 2000 Apr;57(4):485-8. PubMed.
- Lleó A, Blesa R, Queralt R, Ezquerra M, Molinuevo JL, Peña-Casanova J, Rojo A, Oliva R. Frequency of mutations in the presenilin and amyloid precursor protein genes in early-onset Alzheimer disease in Spain. Arch Neurol. 2002 Nov;59(11):1759-63. PubMed.