Abstract
The parkinsonian syndromes comprise a highly heterogeneous group of disorders. Although 15 loci are linked to predominantly familial Parkinson's disease (PD), additional PD loci are likely to exist. We recently identified a multigenerational family of Danish and German descent in which five males in three generations presented with a unique syndrome characterized by parkinsonian features and variably penetrant spasticity for which X-linked disease transmission was strongly suggested (XPDS). Autopsy in one individual failed to reveal synucleinopathy; however, there was a significant four-repeat tauopathy in the striatum. Our objective was to identify the locus responsible for this unique parkinsonian disorder. Members of the XPDS family were genotyped for markers spanning the X chromosome. Two-point and multipoint linkage analyses were performed and the candidate region refined by analyzing additional markers. A multipoint LODmax score of 2.068 was obtained between markers DXS991 and DXS993. Haplotype examination revealed an ∼20 cM region bounded by markers DXS8042 and DXS1216 that segregated with disease in all affected males and obligate carrier females and was not carried by unaffected at-risk males. To reduce the possibility of a false-positive linkage result, multiple loci and genes associated with other parkinsonian or spasticity syndromes were excluded. In conclusion, we have identified a unique X-linked parkinsonian syndrome with variable spasticity and four-repeat tau pathology, and defined a novel candidate gene locus spanning ∼28 Mb from Xp11.2-Xq13.3.
Original language | English (US) |
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Pages (from-to) | 1409-1417 |
Number of pages | 9 |
Journal | Movement Disorders |
Volume | 25 |
Issue number | 10 |
DOIs | |
State | Published - Jul 30 2010 |
Keywords
- Genetic linkage
- Parkinson's disease/Parkinsonism
- Tauopathy
- X-linked Parkinsonism
- X-linked spastic paraparesis
ASJC Scopus subject areas
- Neurology
- Clinical Neurology