The effect of tau genotype on clinical features in FTDP-17.
The clinical phenotype of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) varies. This variability is seen not only between kindreds with different mutations but also in families sharing the same mutation. Inheritance of tau haplotype (H1) and genotype (H1/H1) has been established as a risk factor for some neurodegenerative disorders with parkinsonism. We assessed the effect of tau polymorphism on the clinical features of FTDP-17 in 61 cases from 30 separately ascertained families with four different tau mutations, including P301L, +16, N279K, and P301S. There were no significant differences of age at symptomatic onset and disease duration between H1/H1 and H1/H2 genotypes. The comparison between tau genotype and type of initial clinical sign showed an association between the H1/H1 genotype and parkinsonian phenotype and between the H1/H2 genotype and frontotemporal dementia phenotype (OR=11.7; 95% confidence interval, 1.4-98.7; P=0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17.
Baba
Yasuhiko
Y
Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Tsuboi
Yoshio
Y
Baker
Matthew C
MC
Uitti
Ryan J
RJ
Hutton
Michael L
ML
Dickson
Dennis W
DW
Farrer
Matthew
M
Putzke
John D
JD
Woodruff
Bryan K
BK
Ghetti
Bernardino
B
Murrell
Jill R
JR
Boeve
Bradley F
BF
Petersen
Ronald C
RC
Verpillat
Patrice
P
Brice
Alexis
A
Delisle
Marie-Bernadette
MB
Rascol
Oliver
O
Arima
Kunimasa
K
Dysken
Maurice W
MW
Yasuda
Minoru
M
Kobayashi
Tomonori
T
Sunohara
Nobuhiko
N
Komure
Osamu
O
Kuno
Sadako
S
Sperfeld
Anne D
AD
Stoppe
Gabriela
G
Kohlhase
Jürgen
J
Pickering-Brown
Stuart
S
Neary
David
D
Bugiani
Orso
O
Wszolek
Zbigniew K
ZK
D000328:Adult; D017668:Age of Onset; D003704:Dementia / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000235:genetics*; D010641:Phenotype; D016875:tau Proteins / Q000235:genetics*
C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D016875:tau Proteins