Periaxin mutations cause a broad spectrum of demyelinating neuropathies

Takashima, Hiroshi; Boerkoel, Cornelius F.; Jonghe, Peter De; Ceuterick, C.; Martin, Jean‐Jacques; Voït, Thomas; Schröder, Johann Michael; Williams, Anna; Brophy, Peter; Timmerman, Vincent; Lupski, James R.

doi:10.1002/ana.10213

Cited by 110 publications

(87 citation statements)

References 23 publications

(40 reference statements)

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“…Similar clinical manifestations are observed in patients carrying mutations in different genes, while variable presentations are present even in patients with an identical mutation in the same gene. Recently, there have been several reports that the periaxin (PRX) mutations were detected in the patients showing early onset of symptoms, but with slow or no progression (Boerkoel et al 2001;Guilbot et al 2001;Takashima et al 2002;Kijima et al 2004). We found heterozygous R1070X and L132fsX153 compound mutations of PRX in another patient showing early onset but no progressive clinical symptoms.…”

Section: Introductionmentioning

confidence: 60%

“…L-periaxin has four characteristic domains: PDZ, NLS, repeat and acidic domains (Gillespie et al 1994;Sherman and Brophy 2000;Sherman et al 2001). To date, nine pedigrees, carrying ten nonsense or frameshift mutations of PRX, have been reported (Boerkoel et al 2001;Guilbot et al 2001;Takashima et al 2002;Kijima et al 2004). It is interesting to note that all nine mutations are predicted to produce mutant proteins that lack an acidic domain.…”

Section: Discussionmentioning

confidence: 99%

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Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease

et al. 2006

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Periaxin (PRX) plays an important role in the myelination of the peripheral nerve and consequently in the pathogenesis of Charcot-Marie-Tooth disease (CMT). To date, nine nonsense or frameshift PRX mutations have been reported in eight families with CMT. The patients with PRX mutations appeared to show characteristic clinical features with early onset but slow or no progression, a common result of mutations that lead to missing a C-terminal acidic domain. Here, we report a Japanese CMT patient with these characteristic clinical features, who was a compound heterozygote for PRX R1070X and L132FsX153 mutations. We previously reported that three Japanese isolated families also had the homozygous R1070X mutation. To examine the potential founder effect of the R1070X mutation in the Japanese population, we performed haplotype analysis and found that each R1070X allele lay on a different haplotype background in these four families. Therefore, the high frequency of the R1070X mutation among the Japanese population is not likely the consequence of a founder effect, but probably a result of a mutation hot spot.

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Section: Introductionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease

et al. 2006

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“…Among the 479 DEGs downregulated at 10 dpi, 120 DEGs mapped to "nervous system development" and "neurogenesis" (Table 2). In addition to GFAP, which was the most downregulated gene (FC of 75), other notable DEGs mapping to these GO terms include periaxin (PRX, FC of 20, important for the ensheathment of neurons and axons [89]), CPLX1 (FC of 16, regulating synaptic vesicle exocytosis), and proprotein convertase subtilisin/kexin type 1 inhibitor (ProSAAS, FC of 17, neural tissue inhibitor of prohormone convertase 1, which is involved in insulin synthesis [90]). …”

Section: Fig 7 Immunohistochemistry Gene Validation Ihc Staining Andmentioning

confidence: 99%

Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

Arnold

Girke

Sureshchandra

et al. 2016

J Virol

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Primary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100. SVV DNA and transcripts were detected in sensory ganglia 3 dpi, before the appearance of rash. CD4 and CD8 T cells were also detected in the sensory ganglia 3 dpi. Moreover, lung-resident T cells isolated from the same animals 3 dpi also harbored SVV DNA and transcripts, suggesting that T cells may be responsible for trafficking SVV to the ganglia. Transcriptome sequencing (RNA-Seq) analysis showed that cessation of viral transcription 7 dpi coincides with a robust antiviral innate immune response in the ganglia. Interestingly, a significant number of genes that play a critical role in nervous system development and function remained downregulated into latency. These studies provide novel insights into host-pathogen interactions in the sensory ganglia during acute varicella and demonstrate that SVV infection results in profound and sustained changes in neuronal gene expression. IMPORTANCEMany aspects of VZV infection of sensory ganglia remain poorly understood, due to limited access to human specimens and the fact that VZV is strictly a human virus. Infection of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, provides a robust model of the human disease. Using this model, we show that SVV reaches the ganglia early after infection, most likely by T cells, and that the induction of a robust innate immune response correlates with cessation of virus transcription. We also report significant changes in the expression of genes that play an important role in neuronal function. Importantly, these changes persist long after viral replication ceases. Given the homology between SVV and VZV, and the genetic and physiological similarities between rhesus macaques and humans, our results provide novel insight into the interactions between VZV and its human host and explain some of the neurological consequences of VZV infection. V aricella-zoster virus (VZV) is a neurotropic alphaherpesvirus and the causative agent of varicella (chickenpox) (1). VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster (shingles), a painful disease that affects almost 1 million individuals in the United States alone (2). VZV is transmitted through the inhalation of virus-laden saliva droplets or by direct contact with the infectious fluid from vesicles...

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“…Resulta de mutações no gene da periaxina (PRX), localizado no cromossomo 19q13.1-13.2 55,56 . Seus 2 subcomponentes (periaxina L e S) são essenciais para a formação e manutenção da mielina periférica 57 .…”

Section: Cmt4funclassified

Fenótipos Raros de Neuropatia Hereditária: Charcot-Marie-Tooth Tipo 4

Gondim

Oliveira

Araújo³

et al. 2014

RNC

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RESUMOIntrodução. A Doença de Charcot-Marrie-Tooth (CMT) compreende um grupo geneticamente heterogêneo de neuropatias sensitivo--motoras hereditárias autossômicas dominantes, recessivas e ligadas ao cromossomo X. Objetivo. O objetivo do presente trabalho é realizar uma revisão de literatura a respeito dos principais tipos de CMT4 (variantes desmielinizantes autossômicas recessivas de CMT). Método. Foi realizada uma ampla revisão de literatura buscando artigos originais em inglês (ou pelo menos com resumo em inglês), com descrição das características clínicas, distribuição étnica e geográfica das diversas variantes de CMT4 através das ferramentas OMIM e pubmed da base de dados da NCBI. Resultados. Identificamos e descrevemos os genes, características clínicas, distribuição étnica e geográfica de 12 variantes de CMT4: A,

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Periaxin mutations cause a broad spectrum of demyelinating neuropathies

Cited by 110 publications

References 23 publications

Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease

Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease

Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

Fenótipos Raros de Neuropatia Hereditária: Charcot-Marie-Tooth Tipo 4

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