A 71‐nucleotide deletion in the periaxin gene in a Romani patient with early‐onset slowly progressive demyelinating CMT

Baránková, Lucia; Šišková, Dana; Hühne, Kathrin; Vyhnálková, Emílie; Sakmaryová, Iva; Bojar, Martin; Rautenstrauss, Bernd; Seeman, Pavel

doi:10.1111/j.1468-1331.2008.02104.x

Cited by 16 publications

(13 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, 7 of these SNVs were in exon 7, where the majority of known CMT mutations are found. [29][30][31][32][33] However, none of the identified rare variants was reported previously in Mendelian CMT families. We also did not identify compound heterozygous variation in our patients as would be expected in CMT patients.…”

Section: Snvs In Prxmentioning

confidence: 89%

Sequencing of Charcot–Marie–Tooth disease genes in a toxic polyneuropathy

Beutler

Kulkarni

Kanwar

et al. 2014

Annals of Neurology

View full text Add to dashboard Cite

Objective Mutations in Charcot-Marie-Tooth disease (CMT) genes are the cause of rare familial forms of polyneuropathy. Whether allelic variability in CMT genes is also associated with common forms of polyneuropathy—considered “acquired” in medical parlance—is unknown. Chemotherapy induced peripheral neuropathy (CIPN) occurs commonly in cancer patients and is individually unpredictable. We used CIPN as clinical model to investigate the association of non-CMT polyneuropathy with CMT genes. Methods 269 neurologically asymptomatic cancer patients were enrolled in the clinical trial Alliance N08C1 to receive the neurotoxic drug paclitaxel, while undergoing prospective assessments for polyneuropathy. 49 CMT genes were analyzed by targeted massively parallel sequencing of genomic DNA from patient blood. Results 119 (of 269) patients were identified from the two ends of the polyneuropathy phenotype distribution: patients that were most- and least susceptible to paclitaxel polyneuropathy. The CMT gene PRX was found to be deleteriously mutated in patients who were susceptible to CIPN but not in controls (p=8×10−3). Genetic variation in another CMT gene, ARHGEF10, was highly significantly associated with CIPN (p=5×10−4). Three non-synonymous recurrent single nucleotide variants contributed to the ARHGEF10 signal: rs9657362, rs2294039, and rs17683288. Of these, rs9657362 had the strongest effect (odds ratio of 4.8, p=4×10−4). Interpretation The results reveal an association of CMT gene allelic variability with susceptibility to CIPN. The findings raise the possibility that other acquired polyneuropathies may also be co-determined by genetic etiological factors, of which some may be related to genes already known to cause the phenotypically related Mendelian disorders of CMT.

show abstract

Section: Snvs In Prxmentioning

confidence: 89%

Sequencing of Charcot–Marie–Tooth disease genes in a toxic polyneuropathy

Beutler

Kulkarni

Kanwar

et al. 2014

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…The deletion and substitution mutation of the acidic domain establishes loss-of-function mutations in PRX, causing CMT disease. 15,22,23 The self-interaction in L-PRX is blocked by the E1259K mutation in the acidic domain. The amino acid E1259 could be directly involved in the interaction between the NLS and acidic domain; its mutation results in structural L-PRX damage, which possibly causes the E1259K mutation, leading to recessive Dejerine-Sottas neuropathy.…”

Section: Discussionmentioning

confidence: 99%

“…21 Deletion mutation of the acidic domain causes Charcot-Marie-Tooth disease, type 4F (CMT4F). 22 PRX mutation analysis in neuropathy patients showed that recessive Dejerine-Sottas neuropathy is caused by R1132G, E1259K, E1359del and R1070X mutations in the acidic domain. 15,23 In this study, a series of N-and C-terminally truncated L-PRX constructs were used to investigate the relationship of the structure and function of L-PRX.…”

Section: Introductionmentioning

confidence: 99%

Retracted Article: Self-association of L-periaxin occursviaits acidic domain and NLS2/NLS3, and affects its trafficking in RSC96 cells

2017

View full text Add to dashboard Cite

show abstract

“…10,18 Several lines of evidence indicated that the periaxin protein's function is directly related to CMT4F disease. 10,18 Several lines of evidence indicated that the periaxin protein's function is directly related to CMT4F disease.…”

Section: Discussionmentioning

confidence: 99%

“…10,18 Several lines of evidence indicated that the periaxin protein's function is directly related to CMT4F disease. 15,18,19 An embryonic age (E) of 13.5 is the earliest time at which Lperiaxin is detectable by immunocytochemistry in the nucleus (adaxonal membrane) of Schwann cells of the mouse PNS. 15,18,19 An embryonic age (E) of 13.5 is the earliest time at which Lperiaxin is detectable by immunocytochemistry in the nucleus (adaxonal membrane) of Schwann cells of the mouse PNS.…”

Section: Discussionmentioning

confidence: 99%

Retracted Article: Spectrin-like domain 2 of DRP2 serves as a novel binding region for the NLS2 and 3 sub-domains of L-periaxin

Yang

Shi

2015

RSC Adv.

View full text Add to dashboard Cite

L-periaxin is an important scaffolding protein that is expressed in Schwann cells and lens fiber cells. In Schwann cells, loss or mutation of the PRX gene disrupts compact peripheral myelin and causes severe demyelination neuropathy. DRP2 is the only reported protein to interact with periaxin to form the Lperiaxin-DRP2-dystroglycan (PDG) complex, which can provide structural and signaling functions by linking the extracellular matrix to the Schwann cell cytoskeleton. In this report, the interaction between L-periaxin and DRP2 was further investigated by bimolecular fluorescence complementation (BiFC), GST pull-down, CO-IP, and fluorescence spectroscopy. Results demonstrated that spectrin-like domain 2 of DRP2 played a critical role in the complex of DRP2 and L-periaxin. Furthermore, the DRP2 spectrin-like domain 2 only interacted with the NLS2 and NLS3 sub-domains in L-periaxin. These data revealed a previously unknown binding model between DRP2 and L-periaxin. performed and analyzed the experiments results and wrote the paper, Yawei Shi conceived, designed, coordinated and modied the paper. All authors reviewed the results and approved the nal version of the manuscript. AbbreviationsDRP2 Dystroglycan-dystrophin-related proteins NLS Nuclear-localization-signal CMT Charcot-Marie-Tooth EPPD Ezrin-periplakin-periaxin-desmoyokin PDZ PSD-95/Discs Large/ZO-1 NES Nuclear export signal LMB Leptomycin B PNS Peripheral nervous system PDG L-periaxin-DRP2-dystroglycan EGFP Enhanced green uorescent protein YFP Yellow uorescent protein RFP Red uorescent protein GST Glutathione S-transferase BiFC Bimolecular uorescence complementation Co-IP Co-immunoprecipitation DAPI 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride FITC Fluorescein isothiocyanate This journal is

show abstract

A 71‐nucleotide deletion in the periaxin gene in a Romani patient with early‐onset slowly progressive demyelinating CMT

Abstract: We identified a novel homozygous mutation c.3286_3356del71 (K1095fsX18) in one Romani patient showing very slow disease progression. Amongst non-Romani Czech CMT patients, PRX mutations have been proven to be very rare.

Cited by 16 publications

References 14 publications

Sequencing of Charcot–Marie–Tooth disease genes in a toxic polyneuropathy

Sequencing of Charcot–Marie–Tooth disease genes in a toxic polyneuropathy

Retracted Article: Self-association of L-periaxin occursviaits acidic domain and NLS2/NLS3, and affects its trafficking in RSC96 cells

Retracted Article: Spectrin-like domain 2 of DRP2 serves as a novel binding region for the NLS2 and 3 sub-domains of L-periaxin

Contact Info

Product

Resources

About