Clinical and molecular characterisation of a Parkinson family with a novel PINK1 mutation.
Homozygous mutations in the PINK1 gene have been shown to cause early-onset parkinsonism. Here, we describe a novel homozygous mutation (Q126P), identified in two affected German sisters with a clinical phenotype typical for PINK1-associated parkinsonism. We analysed lactate, pyruvate, carnitine and acylcarnitine blood levels, lactate levels under exercise and in the cerebrospinal fluid, activity of respiratory chain complexes I-IV in muscle biopsies and proteasomal activity in immortalized lymphoblasts, but found no evidence for mitochondrial or proteasomal dysfunction. MR spectroscopy revealed raised myoinositol levels in the basal ganglia of both patients, reflecting possible astroglial proliferation.
Prestel
Jügen
J
Hertie-Institute for Clinical Brain Research, Dept. for Neurodegenerative Diseases, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany.
Gempel
Klaus
K
Hauser
Till-Karsten
TK
Schweitzer
Katherine
K
Prokisch
Holger
H
Ahting
Uwe
U
Freudenstein
Dirk
D
Bueltmann
Eva
E
Naegele
Thomas
T
Berg
Daniela
D
Klopstock
Thomas
T
Gasser
Thomas
T
D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002460:Cell Line; D004252:DNA Mutational Analysis; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005858:Germany; D005911:Gliosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007294:Inositol / Q000032:analysis / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000097:blood / Q000175:diagnosis; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D010375:Pedigree; D011494:Protein Kinases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
D015415:Biomarkers; D005819:Genetic Markers; D007294:Inositol; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase