title: Autosomal recessive parkinsonism.
abstract: Several forms of autosomal recessive parkinsonism are known. In three forms, caused by mutations in parkin (PARK2), PINK1 (PARK6), or DJ-1 (PARK7), the phenotype is usually characterized by levodopa-responsive parkinsonism without atypical features. Parkin mutations are most frequent, explaining -50% of the cases with a clinical diagnosis of familial Parkinson's disease compatible with recessive inheritance and onset <45 years, and -15% of the sporadic cases with onset <45. Mutations in PINK1 and DJ-1 are less common, accounting for -1-8%, and -1-2% of the sporadic cases with early-onset. Since point mutations and genomic rearrangements can be present, sequencing and exon dosage are both required for accurate mutational screening of these genes. The phenotype of parkin mutations is characterized by early-onset parkinsonism, good response to levodopa, and benign course. The average onset age is in the 30s, but late-onset cases have been described. The phenotype associated with PINK1 and DJ-1 mutations has been studied in a smaller number of patients but it is overall indistinguishable from that of parkin. Mutations in other genes, including ATP13A2 (PARK9), PLA2G6 (PARK14), and FBX07 (PARK15), cause more rare forms of recessive parkinsonism with very early-onset (<30 years) and usually additional, atypical features (pyramidal, dystonic, ocular movement, and cognitive disturbances). Yet, it is expected that other monogenic forms of parkinsonism will be identified in the future, as mutations in the above-mentioned genes are not found in other patients with similar phenotypes.
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. v.bonifati@erasmusmc.nl
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bonifati
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis / Q000639:trends; D006801:Humans; D009154:Mutation / Q000235:genetics; D020734:Parkinsonian Disorders / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism