Three families with Perry syndrome from distinct parts of the world

Tacik, Paweł; Fiesel, Fabienne C.; Fujioka, Shinsuke; Ross, Owen A.; Pretelt, Felipe; Cardona, Camilo Castañeda; Kidd, Alexa; Hlavac, Michael; Raizis, Anthony; Okun, Michael S.; Traynor, Sharleen; Strongosky, Audrey; Springer, Wolfdieter; Wszołek, Zbigniew K.

doi:10.1016/j.parkreldis.2014.05.004

Cited by 25 publications

(16 citation statements)

References 13 publications

(35 reference statements)

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“…This case has been reported previously as the proband of the Colombian family [19, 20]. She died at age of 60 years due to pneumonia.…”

Section: Figurementioning

confidence: 71%

“…No common founder was predicted by haplotype analysis. After discovery of the gene, four other PS families with DCTN1 mutations were reported from Korea (p.Gly67Asp) [18], the US (Georgia) (p.Gly71Arg) [19], New Zealand (p.Tyr78Cys) [19], and Colombia (p.Gly71Arg) [19, 20], indicating that PS with DCTN1 mutation could be found worldwide.…”

Section: Perry Syndromementioning

confidence: 99%

“…Intracellular inclusions seen in these mice consisted of mutant p150 Glued [62]. PS-related mutant p150 Glued proteins (p.Phe52Leu, p.Gly71Arg, p.Gln74Pro, and p.Tyr78Cys) showed reduced microtubule binding, and some (p.Phe52Leu, p.Gly71Arg, and p.Gln74Pro) formed cytoplasmic inclusions in the transfected cells [5, 19, 31]. The dynactin subunit p50- and p62-immunopositive neuronal cytoplasmic inclusions, which were occasionally co-localized with TDP-43, were seen in the substantia nigra in PS [5].…”

Section: The Relevance Of Dctn1 Mutations To Neurodegenerationmentioning

confidence: 99%

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DCTN1-related neurodegeneration: Perry syndrome and beyond

Konno

Ross

Teive

et al. 2017

Parkinsonism & Related Disorders

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Perry syndrome (PS) is a rare hereditary neurodegenerative disease characterized by autosomal dominant parkinsonism, psychiatric symptoms, weight loss, central hypoventilation, and distinct TDP-43 pathology. The mutated causative gene for PS is DCTN1, which encodes the dynactin subunit p150Glued. Dynactin is a motor protein involved in axonal transport; the p150Glued subunit has a critical role in the overall function. Since the discovery of DCTN1 in PS, it has been increasingly recognized that DCTN1 mutations can exhibit more diverse phenotypes than previously thought. Progressive supranuclear palsy- and/or frontotemporal dementia-like phenotypes have been associated with the PS phenotypes. In addition, DCTN1 mutations were identified in a family with motor-neuron disease before the discovery in PS. In this review, we analyze the clinical and genetic aspects of DCTN1-related neurodegeneration and discuss its pathogenesis. We also describe three families with PS, Canadian, Polish, and Brazilian. DCTN1 mutation was newly identified in two of them, the Canadian and Polish families. The Canadian family was first described in late 1970’s but was never genetically tested. We recently had the opportunity to evaluate this family and to test the gene status of an affected family member. The Polish family is newly identified and is the first PS family in Poland. Although still rare, DCTN1-related neurodegeneration needs to be considered in a differential diagnosis of parkinsonian disorders, frontotemporal dementia, and motor-neuron diseases, especially if there is family history.

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“…This case has been reported previously as the proband of the Colombian family [19, 20]. She died at age of 60 years due to pneumonia.…”

Section: Figurementioning

confidence: 71%

Section: Perry Syndromementioning

confidence: 99%

Section: The Relevance Of Dctn1 Mutations To Neurodegenerationmentioning

confidence: 99%

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DCTN1-related neurodegeneration: Perry syndrome and beyond

Konno

Ross

Teive

et al. 2017

Parkinsonism & Related Disorders

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“…Heterozygous point mutations in the p150glued N-terminus cause rare adult onset neurodegenerative disorders (Lipka et al, 2013 ). Mutations associated with a Parkinsonian disorder (Perry syndrome) afflict microtubule binding and may cause the accumulation of cargo in axon terminals, which may be explained by impaired recruitment of dynactin at microtubule plus-ends in axon terminals (Lloyd et al, 2012 ; Moughamian et al, 2013 ; Tacik et al, 2014 ). Instead a mutation (G59S) associated with a motor neuron disease, is thought to afflict p150Glued stability and to more generally impair dynactin-dynein functions (Lipka et al, 2013 ).…”

Section: Regulators Of Dynein Activity—dynactinmentioning

confidence: 99%

Cytoplasmic dynein and its regulatory proteins in Golgi pathology in nervous system disorders

Jaarsma

Hoogenraad

2015

Front. Neurosci.

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The Golgi apparatus is a dynamic organelle involved in processing and sorting of lipids and proteins. In neurons, the Golgi apparatus is important for the development of axons and dendrites and maintenance of their highly complex polarized morphology. The motor protein complex cytoplasmic dynein has an important role in Golgi apparatus positioning and function. Together, with dynactin and other regulatory factors it drives microtubule minus-end directed motility of Golgi membranes. Inhibition of dynein results in fragmentation and dispersion of the Golgi ribbon in the neuronal cell body, resembling the Golgi abnormalities observed in some neurodegenerative disorders, in particular motor neuron diseases. Mutations in dynein and its regulatory factors, including the dynactin subunit p150Glued, BICD2 and Lis-1, are associated with several human nervous system disorders, including cortical malformation and motor neuropathy. Here we review the role of dynein and its regulatory factors in Golgi function and positioning, and the potential role of dynein malfunction in causing Golgi apparatus abnormalities in nervous system disorders.

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“…Another variant of interest was identified in DCTN1 , which is associated with Perry syndrome, an autosomal dominant neurodegenerative disorder characterized by late-onset parkinsonism. 14 The identified variant is a heterozygous c.35G→A transition in exon 2 of the gene, resulting in a p.T12M substitution that is present in ExAC with a frequency of 0.00003398 (European: 2/64,482, allele frequency = 3.102E-5; Latino: 2/11,478, allele frequency = 0.0001742). It is in a well-conserved region among human, macaque, mouse, and rat, and slightly alters its three-dimensional conformation ( Supplementary Figure S3 ).…”

Section: Resultsmentioning

confidence: 99%