Steele‐Richardson‐Olszewski syndrome in a patient with a single C212Y mutation in the parkin protein

Abstract

Steele-Richardson-Olszewski syndrome (SROS) is a neurodegenerative disorder of unknown aetiology, most frequently sporadic. Familial cases of SROS have been described. An intronic polymorphism of the tau gene is associated with sporadic SROS and mutations of the tau gene are present in atypical cases of SROS. The role of tau has been excluded in other families with pathology proven SROS, suggesting that this syndrome may have multiple causes. An 82-year-old patient, father of 3 children with autosomal recessive juvenile parkinsonism due to combined heterozygous mutations of the parkin gene, developed clinical features of SROS 2 years before death. The diagnosis was confirmed by pathology. He carried the C212Y mutation of the parkin gene and was homozygous for the A0 polymorphism and for the H1 haplotype. The role of parkin in the processing of tau is discussed.

Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1

“…A patient with pathology-proved PSP was found to be a heterozygous carrier of a C212Y mutation of the Park-2 gene, as well as a homozygote for the H1 haplotype of tau. 36 That report provides an interesting link between parkin, a protein with ubiquitin ligase function that plays a role in the processing of tau, and tauopathies, and it offers an explanation for the increased prevalence of parkinsonism in relatives of patients with Parkinson's disease. 36 The locus associated with PSP in the family that we describe here is different from any other region of the human genome involved in PSP or in other related neurodegenerative disorders.…”

“…36 That report provides an interesting link between parkin, a protein with ubiquitin ligase function that plays a role in the processing of tau, and tauopathies, and it offers an explanation for the increased prevalence of parkinsonism in relatives of patients with Parkinson's disease. 36 The locus associated with PSP in the family that we describe here is different from any other region of the human genome involved in PSP or in other related neurodegenerative disorders. The segregation of haplotypes in this family localizes the locus of PSP to 1q31.1, a region of 3.4cM that is not fully investigated.…”

Olfaction in Parkin heterozygotes and compound heterozygotes

“…Only 2 of the 6 homozygotes/compound heterozygotes had Lewy bodies, 33,34 whereas the clinical course and pathology from a single autopsy of a Parkin mutation heterozygote was consistent with progressive supranuclear palsy. 35 Based on our findings of different olfactory performance in Parkin mutation heterozygotes and Parkin compound heterozygotes, we hypothesize that better UPSIT performance is inversely correlated with Lewy body pathology, and that Parkin heterozygotes with PD have Lewy bodies in the olfactory bulb; however, autopsy data are lacking, and further research is required to address the relationship between olfactory performance and the underlying disease mechanism.…”

The multiple mechanisms of amyloid deposition: The role of parkin

“…[44][45][46][47][48] Parkin mutations and parkin polymorphism increase the risk of deposition of tau in progressive supranuclear palsy (PSP). 49,50 Furthermore, in mice overexpressing human mutated tau (Tau VLW ), which in normal conditions do not form amyloid deposits, the suppression To our knowledge, PK -/-/Tau VLW mice are the first model that has developed Aβ pathology without amyloid precursor protein or directly related proteins manipulation. Surprisingly, the amyloid deposits are not restricted to the brain.…”