We cover dopa-responsive dystonia, Wilson's disease, Parkin-, PINK1-, and DJ-1-associated parkinsonism (PARK2, 6, and 7), x-linked dystonia-parkinsonism/Lubag (DYT3), rapid-onset dystonia-parkinsonism (DYT12) and DYT16 dystonia, the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) including pantothenate kinase (PANK2)- and PLA2G6 (PARK14)-associated neurodegeneration, neuroferritinopathy, Kufor-Rakeb disease (PARK9) and the recently described SENDA syndrome; FBXO7-associated neurodegeneration (PARK15), autosomal-recessive spastic paraplegia with a thin corpus callosum (SPG11), and dystonia parkinsonism due to mutations in the SLC6A3 gene encoding the dopamine transporter.
Various deletions and point mutations in the Parkin gene have been strongly associated with Parkinson's disease (PD) and parkinsonism, especially when the onset occurs at a young age.
Using serial (18)F-dopa PET, the present longitudinal study addresses rates of progression of nigrostriatal dysfunction in both compound heterozygous (parkin-linked parkinsonism) and single heterozygous parkin gene carriers.
Two brothers with parkinsonism and deletion of axons 4-6 of the parkin gene (ages 51, 55 years; duration of symptoms, 22, 29 years respectively) and 4 randomly selected patients with YOPD (mean age 47.8+/-4.9 years; mean duration of symptoms, 11.5+/-1.9 years) were administered a neuropsychological battery at "on" state.
To investigate whether the presence of parkin gene mutations is associated with different nigrostriatal impairment than other early-onset parkinsonism.
To describe a large consanguineous family in which inheritance of a 438- to 477-base pair deletion in exon 3 (Ex3Delta40) in the parkin gene resulted in parkinsonism (age range at onset, 24-32 years).
Thus, parkinsonism in parkin gene carriers may be related to abnormal nigral protein accumulation in the presence of a suprathreshold enzyme dysfunction.
These data suggest that compound heterozygous parkin mutations and loss of parkin protein may lead to early-onset parkinsonism with Lewy body pathology, while a hemizygous mutation may confer increased susceptibility to typical Parkinson's disease.
The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD.
Recessively inherited deletions/duplications and point mutations in the parkin gene are the most common cause of early-onset parkinsonism known so far, but in an increasing number of studies, genetic variations in the serine/threonine kinase domain of the PINK1 gene are found to explain early-onset parkinsonism.
Recessively inherited deletions/duplications and point mutations in the parkin gene are the most common cause of early-onset parkinsonism known so far, but in an increasing number of studies, genetic variations in the serine/threonine kinase domain of the PINK1 gene are found to explain early-onset parkinsonism.