ABSTRACT
We analyzed the DJ1 gene in a large consecutive series (N=163) of Italian unrelated Early Onset Parkinson Disease (EOPD: onset ≤40 years of age) patients and 100 healthy controls (mean age 64 ± 7 years). No homozygous or compound heterozygous mutations with an obvious pathogenic effect were found. Several variants were identified, some of which were novels. All variants had similar frequency in patients and in controls. Our data suggest that DJ1 mutations are very rare in Italian EOPD. Other genes and risk factors for PD are still to be identified.
Subject(s)
Intracellular Signaling Peptides and Proteins/genetics , Oncogene Proteins/genetics , Parkinsonian Disorders/genetics , Adolescent , Adult , Cohort Studies , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Humans , Italy , Male , Multiplex Polymerase Chain Reaction , Protein Deglycase DJ-1 , Reverse Transcriptase Polymerase Chain Reaction , White People , Young AdultABSTRACT
We analysed the parkin gene in a large consecutive series (146) of unrelated early onset Parkinson's disease (onset ?40 years of age) patients. Twelve cases (8.2%) had homozygous or compound heterozygous point mutations and/or exon rearrangements, while a single mutation was found in four subjects (2.7%). We identified eight exon rearrangements and nine point mutations, two of which were novel: c.735delT (p.C212/X224) and c.815C>G (p.C238W). Genotype-phenotype correlation revealed that parkin carriers had features similar to those of non-carrier early onset Parkinson disease patients.
Subject(s)
Genetic Predisposition to Disease , Mutation/genetics , Parkinson Disease/genetics , Ubiquitin-Protein Ligases/genetics , Adult , Age of Onset , DNA Mutational Analysis , Exons/genetics , Female , Gene Dosage , Gene Frequency , Genotype , Humans , Male , Phenotype , Severity of Illness Index , Statistics, NonparametricABSTRACT
We analysed the Leucine-Rich Repeat Kinase 2 (LRRK2) gene for the G2019S mutation in 1245 consecutive, unrelated patients with primary degenerative parkinsonism, and collected information on medical history, motor, cognitive and neuropsychiatric functions to characterize the clinical phenotype associated to the G2019S mutation. The mutation was detected in heterozygous state in 19 probands (1.7%), and in five additional affected relatives. Clinical features in carriers were those of typical, idiopathic Parkinson's disease. However, behavioural abnormalities were frequent (87%), suggesting a more widespread limbic involvement in G2019S carriers.
