Mutation analysis of the neurofilament M gene in Parkinson's disease.
Neurofilament M, a major component of Lewy bodies, represents an interesting candidate in the pathogenesis of Parkinson's disease (PD). We performed detailed mutation analyses of the NF-M gene in 322 familial and sporadic PD patients. Two polymorphisms (Ala475Thr and Gly697Arg) occurred at similar frequencies in PD patients and controls. A Pro725Gln substitution and a deletion of valine in position 829 were identified in two PD patients. These substitutions affect residues of the NF-M protein that are highly conserved among different species. None of our patients carried the Gly336Ser substitution, which has been described in familial PD. Our results argue against a major role of NF-M in PD. However, rare variants of the NF-M gene may act as susceptibility factors for PD and functional analyses of the identified variations are warranted to decipher possible mechanisms in neurodegeneration.
Department of Neurology, Neurodegeneration Laboratory, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076, Tübingen, Germany. reijko.krueger@uni-tuebingen.de
Rejko
R
Krüger
Christian
C
Fischer
Thorsten
T
Schulte
Karsten M
KM
Strauss
Thomas
T
Müller
Dirk
D
Woitalla
Daniela
D
Berg
Marcel
M
Hungs
Rene
R
Gobbele
Klaus
K
Berger
Jörg T
JT
Epplen
Olaf
O
Riess
Ludger
L
Schöls
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D016631:Lewy Bodies / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000172:deficiency / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D016900:Neurofilament Proteins; C061195:neurofilament protein M