Genetic Analysis in Patients with Familial and Sporadic Frontotemporal Dementia: Two Tau Mutations in Only Familial Cases and No Association with Apolipoprotein ε4

Abstract

We screened for tau gene mutations among 24 Japanese (6 familial and 18 sporadic cases) and 4 Polish patients with frontotemporal dementia (FTD) using PCR-SSCP analysis followed by DNA sequencing. We identified 2 missense mutations in exon 10: N279K and P301L in 2 Japanese patients with familial FTD. Additionally 3 DNA polymorphisms: 2 known (3′ exon 3 + 9, A → G and exon 7, codon 176, G → A) and 1 new (exon 8, codon 185, T → C) were identified in 1 Polish patient. Tau mutations were not found in subjects with a negative family history suggesting that tau mutations do not account for most sporadic cases of FTD. We also found no association of apolipoprotein E4 allele with FTD.