Clinical features and disease haplotypes of individuals with the N279K tau gene mutation: a comparison of the pallidopontonigral degeneration kindred and a French family.
BACKGROUND
An N279K missense mutation in exon 10 of the tau gene reported in an American family with pallidopontonigral degeneration (PPND family) was recently found in members of a French kindred with dementia and supranuclear palsy.


OBJECTIVE
To compare clinical phenotypes of both families and to perform genealogical and molecular genetic studies to determine whether they are derived from a common founder.


METHODS
We performed clinical examinations of affected members of both families and compared clinical phenotypes, existing genealogical family records, and chromosome 17 microsatellite repeat markers in the vicinity of the tau gene.


RESULTS
The inheritance pattern is autosomal dominant in the PPND family and appears so in the French family. Average age at onset of clinical symptoms was 43 years in the PPND family and 41 years in the French family. Mean disease duration was 8 years in the PPND family and 6 years in the French family. Parkinsonism, personality changes, and dementia of the frontotemporal type were seen in both kindreds. All affected patients exhibited rapidly progressive parkinsonism characterized by bradykinesia, tremor, postural instability, and rigidity. Some had a transient response to levodopa therapy during the initial stages. Pyramidal signs and eye movement abnormalities, including supranuclear gaze palsy, were common. Results of linkage studies of the tau region in chromosome 17 did not reveal a haplotype common to both kindreds.


CONCLUSIONS
Affected members from both families had more clinical similarities than differences. Results of genealogical and molecular genetic studies determined that the families were not related. The N279K mutations found in both families have independent origins.
Tsuboi
Yoshio
Y
Department of Neurology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA.
Uitti
Ryan J
RJ
Delisle
Marie-Bernadette
MB
Ferreira
Joaquim J
JJ
Brefel-Courbon
Christine
C
Rascol
Olivier
O
Ghetti
Bernardino
B
Murrell
Jill R
JR
Hutton
Michael
M
Baker
Matthew
M
Wszolek
Zbigniew K
ZK
D000328:Adult; D001216:Asparagine / Q000235:genetics*; D003704:Dementia / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D013494:Supranuclear Palsy, Progressive / Q000235:genetics* / Q000503:physiopathology; D016875:tau Proteins / Q000235:genetics*
D016875:tau Proteins; D001216:Asparagine; D008239:Lysine