title: Homozygous PINK1 C-terminus mutation causing early-onset parkinsonism.
abstract: Two homozygous mutations in the PINK1 gene, encoding a mitochondrial putative protein kinase, recently have been identified in families with PARK6-linked, autosomal recessive early-onset parkinsonism (AREP). Here, we describe a novel homozygous mutation (1573_1574 insTTAG) identified in an AREP patient, which causes a frameshift and truncation at the C-terminus of the PINK1 protein, outside the kinase catalytic domain. The clinical phenotype includes early-onset (28 years) parkinsonism, foot dystonia at onset, good levodopa response, slow progression, early levodopa-induced dyskinesias, and sleep benefit, thereby resembling closely parkin-related disease. These findings confirm that recessive mutations in PINK1 cause early-onset parkinsonism and expand the associated clinical phenotype.
authors.affiliation: Department of Clinical Genetics, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Christan F
authors.initials: CF
authors.lastname: Rohé
authors.forename: Pasquale
authors.initials: P
authors.lastname: Montagna
authors.forename: Guido
authors.initials: G
authors.lastname: Breedveld
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bonifati
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020734:Parkinsonian Disorders / Q000201:enzymology* / Q000235:genetics*; D010375:Pedigree; D010446:Peptide Fragments / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D010446:Peptide Fragments; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase