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.
Krüger
Rejko
R
Department of Neurology, Neurodegeneration Laboratory, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076, Tübingen, Germany. reijko.krueger@uni-tuebingen.de
Fischer
Christian
C
Schulte
Thorsten
T
Strauss
Karsten M
KM
Müller
Thomas
T
Woitalla
Dirk
D
Berg
Daniela
D
Hungs
Marcel
M
Gobbele
Rene
R
Berger
Klaus
K
Epplen
Jörg T
JT
Riess
Olaf
O
Schöls
Ludger
L
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