title: Marked variation in clinical presentation and age of onset in a family with a heterozygous parkin mutation.
abstract: Parkin gene mutations have been detected in families with early-onset autosomal recessive parkinsonism. We report a novel heterozygous 40 base pair deletion in exon 3 of the parkin gene that increases the susceptibility of carriers to develop parkinsonism/dystonia and manifests remarkable variability in regard to age of onset and phenotype in a single family. After identifying the new mutation in the proband of this kindred, family members were contacted and evaluated by a movement disorders specialist using standardized protocols and prospectively set diagnostic criteria. Importantly, examining physicians and family members were blinded to the genetic testing. Five affected members in two generations carried the parkin mutation. The proband and one of his brothers had disease onset at 24 years of age while another brother had disease at age 44. One exhibited multi-focal dystonia and parkinsonism of 17 years duration, another suffered a unilateral slowly progressive parkinsonism over 13 years while the third suffered dystonia-parkinsonism of recent onset. A sibling pair in the preceding generation had mild previously undiagnosed parkinsonism. Clinicians should be aware that patients carrying a parkin gene mutation may present with dystonia-parkinsonism or very subtle parkinsonism with a markedly varied age of onset.
authors.affiliation: The Parkinson's Institute, Sunnyvale, California 84089, USA.
authors.forename: Louis C
authors.initials: LC
authors.lastname: Tan
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Tanner
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
authors.forename: Matthew
authors.initials: M
authors.lastname: Farrer
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: J William
authors.initials: JW
authors.lastname: Langston
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D020029:Base Pairing / Q000235:genetics; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D003704:Dementia / Q000175:diagnosis* / Q000235:genetics; D003937:Diagnosis, Differential; D018450:Disease Progression; D004198:Disease Susceptibility; D020821:Dystonic Disorders / Q000175:diagnosis / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein