title: Screening for mutations of the HFE gene in Parkinson's disease patients with hyperechogenicity of the substantia nigra.
abstract: Iron mediated oxidative stress is known to contribute to the neurodegenerative process in Parkinson's disease (PD). Although there are hints that genes involved in brain iron metabolism might be involved in the pathogenesis of PD in some instances, it is still not known whether the increase in brain iron content constitutes a primary or secondary event in the disease cascade. Recent studies on the role of hemochromatosis gene (HFE) mutations in PD vary from a protective effect of C282Y heterozygosity, no effect of the C282Y or H63D mutation to an increased risk for PD in C282Y mutation carriers. In this study, analyzing the whole coding region of the HFE gene by dHPLC in 278 PD patients, priorly characterized by transcranial sonography for increased iron content of the substantia nigra (SN), we did not find an association of the common HFE mutations and PD. However, we identified two novel variants (K92N and I217T) each in a single PD patient. These variations were not found in any of the controls. Future studies are necessary to reveal a possible functional relevance of these mutations for PD. Our results indicate that mutations in the HFE gene are not a common cause for PD with increased iron levels of the SN.
authors.affiliation: Institute of Medical Genetics, University of Tuebingen, Tuebingen, Germany.
authors.forename: Nilgün
authors.initials: N
authors.lastname: Akbas
authors.forename: Helmine
authors.initials: H
authors.lastname: Hochstrasser
authors.forename: Joelle
authors.initials: J
authors.lastname: Deplazes
authors.forename: Jürgen
authors.initials: J
authors.lastname: Tomiuk
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Uwe
authors.initials: U
authors.lastname: Walter
authors.forename: Stefanie
authors.initials: S
authors.lastname: Behnke
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
mesh_terms: D000368:Aged; D001224:Aspartic Acid / Q000235:genetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009088:Mucoproteins / Q000235:genetics; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*; D013912:Threonine / Q000235:genetics
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D009088:Mucoproteins; D012333:RNA, Messenger; C010393:lysin, gastropoda; D007532:Isoleucine; D013912:Threonine; D001224:Aspartic Acid