Journal of the Peripheral Nervous System最新文献

{"title":"Correction to ‘Serum neurofilament light chain measurements following nerve trauma’","authors":"","doi":"10.1111/jns.12642","DOIUrl":"10.1111/jns.12642","url":null,"abstract":"<p>Wilcox M, Rayner MLD, Guillemot-Legris O, Platt I, Brown H, Quick T, Phillips JB Serum neurofilament light chain measurements following nerve trauma. J Peripher Nerv Syst. 2023;28(3):500–507. doi:10.1111/jns.12576</p><p>There was an error in the analysis of serum NfL data that resulted in the values in Figure 1, Table 1 and Results being expressed incorrectly as 40-fold lower than their correct concentration. The ‘Serum NfL analysis’ section of the Methods should read ‘Serum NfL concentration was measured using the Simoa HD-X Analyser (Quanterix, Billerica, MA) with a Neurology 4-plex B kit (item number: 103345). All samples were randomised across the plates and run in duplicate. All samples measured were above the lower limit of detection (0.0962 pg/mL) with a mean coefficient of variation of 13.2% between duplicates. Intra- and inter-plate coefficients of variation, monitored using 2-4 pooled human internal control samples across each plate, were &lt;10%’. not ‘NfL levels in serum were measured using a SIMOA® SR-X analyser (Quanterix Corporation, Massachusetts) with a SIMOA® NF-light Advantage (SR-X) Kit (Quanterix, No. 103400) according to protocols well described elsewhere (O'Brien, et al., 2021). All samples were run in duplicate and analysers were blinded to the experimental conditions. All samples measured above the lower limit of detection (0.038 pg/mL) with a mean coefficient of variation of 9.15% between duplicates. Furthermore, two control samples were run on each place with a mean coefficient of variation of 6.90%’.</p><p>New versions of Figure 1 and Table 1 have been provided. In addition, the second line of the Results section should read 20.33 ± 8.98 pg/mL rather than 0.50 ± 0.2 pg/mL. The third line of the Discussion section should read 20 pg/mL rather than 0.50 pg/mL.</p><p>We apologise for this error.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"376-377"},"PeriodicalIF":3.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of eculizumab in Guillain-Barré syndrome: A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial","authors":"Satoshi Kuwabara,&nbsp;Susumu Kusunoki,&nbsp;Motoi Kuwahara,&nbsp;Yoshihisa Yamano,&nbsp;Yoichiro Nishida,&nbsp;Hirokazu Ishida,&nbsp;Tomoyuki Kasuya,&nbsp;Erik Kupperman,&nbsp;Qun Lin,&nbsp;Glen Frick,&nbsp;Sonoko Misawa","doi":"10.1111/jns.12646","DOIUrl":"10.1111/jns.12646","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Guillain-Barré syndrome (GBS) is an acute, self-limited, immune-mediated peripheral neuropathy. Current treatments for GBS include intravenous immunoglobulin (IVIg) and plasma exchange, which may not sufficiently benefit severely affected patients. This study evaluated the efficacy and safety of eculizumab add-on therapy to IVIg (standard-of-care treatment) in patients with severe GBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial (NCT04752566), enrolled Japanese adults (age ≥ 18 years) with severe GBS (Hughes functional grade [FG] score FG3 or FG4/FG5 within 2 weeks of onset of GBS). Participants were randomized 2:1 to receive intravenous infusion of eculizumab or placebo (once weekly for 4 weeks) with IVIg treatment with 20 weeks of follow-up. Primary efficacy endpoint was the time to first reach FG score ≤1 (able to run). Key secondary endpoints were proportion of participants achieving FG ≤1 at weeks 8 and 24 and FG improvement ≥3 at week 24. Pharmacodynamic analysis of serum free C5 concentration over time was performed. Safety was evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The analysis included 57 participants (eculizumab, <i>n</i> = 37; placebo, <i>n</i> = 20). Primary endpoint was not achieved (hazard ratio, 0.9; 95% CI, 0.45–1.97; <i>p</i> = .89). Key secondary endpoints did not reach statistical significance. Serum C5 concentration was reduced by 99.99% at 1 h postdose and sustained to week 5 but returned to baseline at the end of follow-up period. No new safety signals for eculizumab were identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Although well tolerated, eculizumab treatment did not show significant effects on motor function recovery compared to placebo in patients with GBS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"339-349"},"PeriodicalIF":3.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12646","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, histologic, and immunologic signatures of Small Fiber Neuropathy in Systemic Lupus Erythematosus","authors":"Eleonora Galosi,&nbsp;Carmelo Pirone,&nbsp;Fulvia Ceccarelli,&nbsp;Nicoletta Esposito,&nbsp;Pietro Falco,&nbsp;Martina Leopizzi,&nbsp;Valeria Di Maio,&nbsp;Lorenzo Tramontana,&nbsp;Gianfranco De Stefano,&nbsp;Giuseppe Di Pietro,&nbsp;Giulia Di Stefano,&nbsp;Cristina Garufi,&nbsp;Caterina Leone,&nbsp;Francesco Natalucci,&nbsp;Valeria Orefice,&nbsp;Cristiano Alessandri,&nbsp;Francesca Romana Spinelli,&nbsp;Andrea Truini,&nbsp;Fabrizio Conti","doi":"10.1111/jns.12644","DOIUrl":"10.1111/jns.12644","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Systemic Lupus Erythematosus (SLE) often causes damage to small nerve fibers, leading to distressing painful and autonomic symptoms. Despite this, Small Fiber Neuropathy (SFN) remains an underrecognized complication for SLE patients. In this cross-sectional study, we aimed to assess SFN in patients with SLE and to explore its correlations with immunologic disease features and clinical manifestations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 50 SLE patients (1 male to 12.5 females, aged 20–80 years) reporting painful disturbances. We conducted a comprehensive clinical and neurophysiological evaluation, using Nerve Conduction Studies and Quantitative Sensory Testing. Additionally, we carried out an extensive laboratory assessment of disease-related serological parameters. We also performed a thorough skin biopsy analysis, investigating somatic and autonomic innervation while detecting complement and inflammatory cell infiltrates within the skin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 50 patients, 19 were diagnosed with SFN, primarily characterized by a non-length-dependent distribution; 7 had a mixed neuropathy, with both large and small fiber involvement. Patients with SFN were younger than patients with a mixed neuropathy (<i>p</i> = .0143); furthermore, they were more likely to have a history of hypocomplementemia (<i>p</i> = .0058) and to be treated with cyclosporine A (<i>p</i> = .0053) compared to patients without neuropathy. However, there were no significant differences in painful and autonomic symptoms between patients with and without SFN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>This study highlights the relevant frequency of SFN with a non-length-dependent distribution among SLE patients experiencing painful symptoms. Indeed, SFN emerges as an early manifestation of SLE-related neuropathy and is closely associated with hypocomplementemia, suggesting a potential pathogenic role of the complement system. Moreover, SFN may be influenced by disease-modifying therapies. However, the precise role of SFN in shaping painful and autonomic symptoms in patients with SLE remains to be fully elucidated.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"315-328"},"PeriodicalIF":3.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of cellular and noncellular components of mature intact human peripheral nerve","authors":"Gabriela I. Aparicio,&nbsp;Jorge E. Quintero,&nbsp;Lauren Plum,&nbsp;Lingxiao Deng,&nbsp;Kristen Wanczyk,&nbsp;Miriam Henry,&nbsp;Evan Lynch,&nbsp;Michael Murphy,&nbsp;Greg A. Gerhardt,&nbsp;Craig G. van Horne,&nbsp;Paula V. Monje","doi":"10.1111/jns.12643","DOIUrl":"10.1111/jns.12643","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The goal of this study was to define basic constituents of the adult peripheral nervous system (PNS) using intact human nerve tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We combined fluorescent and chromogenic immunostaining methods, myelin-selective fluorophores, and routine histological stains to identify common cellular and noncellular elements in aldehyde-fixed nerve tissue sections. We employed Schwann cell (SC)-specific markers, such as S100β, NGFR, Sox10, and myelin protein zero (MPZ), together with axonal, extracellular matrix (collagen IV, laminin, fibronectin), and fibroblast markers to assess the SC's relationship to myelin sheaths, axons, other cell types, and the acellular environment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Whereas S100β and Sox10 revealed mature SCs in the absence of other stains, discrimination between myelinating and non-myelinating (Remak) SCs required immunodetection of NGFR along with axonal and/or myelin markers. Surprisingly, our analysis of NGFR+ profiles uncovered the existence of at least 3 different novel populations of NGFR+/S100β− cells, herein referred to as nonglial cells, residing in the stroma and perivascular areas of all nerve compartments. An important proportion of the nerve's cellular content, including circa 30% of endoneurial cells, consisted of heterogenous S100β negative cells that were not associated with axons. Useful markers to identify the localization and diversity of nonglial cell types across different compartments were Thy1, CD34, SMA, and Glut1, a perineurial cell marker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our optimized methods revealed additional detailed information to update our understanding of the complexity and spatial orientation of PNS-resident cell types in humans.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"294-314"},"PeriodicalIF":3.9,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corneal confocal microscopy detects early nerve regeneration after pharmacological and surgical interventions: Systematic review and meta-analysis","authors":"Hoda Gad,&nbsp;Einas Elgassim,&nbsp;Ahamed Lebbe,&nbsp;Ross S. MacDonald,&nbsp;Areej Baraka,&nbsp;Ioannis N. Petropoulos,&nbsp;Georgios Ponirakis,&nbsp;Nada O. Ibrahim,&nbsp;Rayaz A. Malik","doi":"10.1111/jns.12641","DOIUrl":"10.1111/jns.12641","url":null,"abstract":"<p>Corneal confocal microscopy (CCM) is an ophthalmic imaging technique that enables the identification of corneal nerve fibre degeneration and regeneration. To undertake a systematic review and meta-analysis of studies utilizing CCM to assess for corneal nerve regeneration after pharmacological and surgical interventions in patients with peripheral neuropathy. Databases (EMBASE [Ovid], PubMed, CENTRAL and Web of Science) were searched to summarize the evidence from randomized and non-randomized studies using CCM to detect corneal nerve regeneration after pharmacological and surgical interventions. Data synthesis was undertaken using RevMan web. Eighteen studies including 958 patients were included. CCM identified an early (1–8 months) and longer term (1–5 years) increase in corneal nerve measures in patients with peripheral neuropathy after pharmacological and surgical interventions. This meta-analysis confirms the utility of CCM to identify nerve regeneration following pharmacological and surgical interventions. It could be utilized to show a benefit in clinical trials of disease modifying therapies for peripheral neuropathy.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"173-184"},"PeriodicalIF":3.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal gammopathy-associated peripheral neuropathies: Uncovering pearls and challenges","authors":"Trajano Aguiar Pires Gonçalves,&nbsp;Camila Derminio Donadel,&nbsp;Rodrigo Siqueira Soares Frezatti,&nbsp;Pedro Manoel Marques Garibaldi,&nbsp;Rodrigo T. Calado,&nbsp;Wilson Marques Junior,&nbsp;Pedro José Tomaselli","doi":"10.1111/jns.12638","DOIUrl":"10.1111/jns.12638","url":null,"abstract":"<p>Monoclonal gammopathy-related peripheral neuropathies encompass a spectrum of clinical presentations in which the monoclonal protein directly damages the tissues, including the peripheral nervous system. Given the prevalence of both peripheral neuropathy and monoclonal gammopathy in the general population, these conditions may overlap in clinical practice, posing a challenge for clinicians in determining causality. Therefore, a comprehensive understanding of primary clinical syndromes and their neurophysiological patterns is of great importance for accurate differential diagnoses and effective treatment strategies. In this article, we examine the main forms of monoclonal gammopathies that affect the peripheral nerve. We explore the clinical and electrophysiological aspects and their correlation with each syndrome's corresponding monoclonal protein type. This knowledge is essential for healthcare professionals to diagnose better and manage patients presenting with monoclonal gammopathy-related peripheral nervous system involvement.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"161-172"},"PeriodicalIF":3.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neurological core features of the infantile-onset multisystem neurologic, endocrine, and pancreatic disease: A novel nonsense mutation in an Italian family","authors":"Alessia Mammi,&nbsp;Alessandro Geroldi,&nbsp;Serena Patrone,&nbsp;Fabio Gotta,&nbsp;Paola Origone,&nbsp;Andrea Gaudio,&nbsp;Andrea La Barbera,&nbsp;Francesca Sanguineri,&nbsp;Clarissa Ponti,&nbsp;Michele Iacomino,&nbsp;Monica Traverso,&nbsp;Edoardo Ferlazzo,&nbsp;Angelo Schenone,&nbsp;Angelo Pascarella,&nbsp;Oreste Marsico,&nbsp;Paola Mandich,&nbsp;Emilia Bellone","doi":"10.1111/jns.12636","DOIUrl":"10.1111/jns.12636","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Biallelic mutations in the <i>PTRH2</i> gene have been associated with infantile multisystem neurological, endocrine, and pancreatic disease (IMNEPD), a rare autosomal recessive disorder of variable expressivity characterized by global developmental delay, intellectual disability or borderline IQ level, sensorineural hearing loss, ataxia, and pancreatic insufficiency. Various additional features may be included, such as peripheral neuropathy, facial dysmorphism, hypothyroidism, hepatic fibrosis, postnatal microcephaly, cerebellar atrophy, and epilepsy. Here, we report the first Italian family presenting only predominant neurological features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Extensive neurological and neurophysiological evaluations have been conducted on the two affected brothers and their healthy mother since 1996. The diagnosis of peripheral neuropathy of probable hereditary origin was confirmed through a sural nerve biopsy. Exome sequencing was performed after the analysis of major neuropathy-associated genes yielded negative results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Whole-exome sequencing analysis identified the homozygous substitution c.256C&gt;T (p.Gln86Ter) in the <i>PTRH2</i> gene in the two siblings. According to American College of Medical Genetics and Genomics (ACMG) guidelines, the variant has been classified as pathogenic.</p>\u0000 \u0000 <p>At 48 years old, the proband's reevaluation confirmed a demyelinating sensorimotor polyneuropathy with bilateral sensorineural hearing loss that had been noted since he was 13. Additionally, drug-resistant epileptic seizures occurred when he was 32 years old. No hepatic or endocrinological signs developed. The younger affected brother, 47 years old, has an overlapping clinical presentation without epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our findings expand the clinical phenotype and further demonstrate the clinical heterogeneity related to <i>PTRH2</i> variants. We thereby hope to better define IMNEPD and facilitate the identification and diagnosis of this novel disease entity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"279-285"},"PeriodicalIF":3.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to the Letter to the Editor “Do corticosteroids aggravate pure motor chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)?” by Kokubun N. et al.","authors":"P. Y. K. van den Bergh,&nbsp;P. A. van Doorn,&nbsp;R. D. M. Hadden,&nbsp;the EAN/PNS CIDP guideline – second revision Task Force members","doi":"10.1111/jns.12640","DOIUrl":"10.1111/jns.12640","url":null,"abstract":"","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"288-289"},"PeriodicalIF":3.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A deep intronic variant in MME causes autosomal recessive Charcot–Marie–Tooth neuropathy through aberrant splicing","authors":"Bianca R. Grosz,&nbsp;Jevin M. Parmar,&nbsp;Melina Ellis,&nbsp;Samantha Bryen,&nbsp;Cas Simons,&nbsp;Andre L. M. Reis,&nbsp;Igor Stevanovski,&nbsp;Ira W. Deveson,&nbsp;Garth Nicholson,&nbsp;Nigel Laing,&nbsp;Mathew Wallis,&nbsp;Gianina Ravenscroft,&nbsp;Kishore R. Kumar,&nbsp;Steve Vucic,&nbsp;Marina L. Kennerson","doi":"10.1111/jns.12637","DOIUrl":"10.1111/jns.12637","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Loss-of-function variants in <i>MME</i> (membrane metalloendopeptidase) are a known cause of recessive Charcot–Marie–Tooth Neuropathy (CMT). A deep intronic variant, <i>MME</i> c.1188+428A&gt;G (NM_000902.5), was identified through whole genome sequencing (WGS) of two Australian families with recessive inheritance of axonal CMT using the seqr platform. <i>MME</i> c.1188+428A&gt;G was detected in a homozygous state in Family 1, and in a compound heterozygous state with a known pathogenic <i>MME</i> variant (c.467del; p.Pro156Leufs*14) in Family 2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We aimed to determine the pathogenicity of the <i>MME</i> c.1188+428A&gt;G variant through segregation and splicing analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The splicing impact of the deep intronic <i>MME</i> variant c.1188+428A&gt;G was assessed using an in vitro exon-trapping assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The exon-trapping assay demonstrated that the <i>MME</i> c.1188+428A&gt;G variant created a novel splice donor site resulting in the inclusion of an 83 bp pseudoexon between <i>MME</i> exons 12 and 13. The incorporation of the pseudoexon into <i>MME</i> transcript is predicted to lead to a coding frameshift and premature termination codon (PTC) in <i>MME</i> exon 14 (p.Ala397ProfsTer47). This PTC is likely to result in nonsense mediated decay (NMD) of <i>MME</i> transcript leading to a pathogenic loss-of-function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>To our knowledge, this is the first report of a pathogenic deep intronic <i>MME</i> variant causing CMT. This is of significance as deep intronic variants are missed using whole exome sequencing screening methods. Individuals with CMT should be reassessed for deep intronic variants, with splicing impacts being considered in relation to the potential pathogenicity of variants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"262-274"},"PeriodicalIF":3.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do corticosteroids aggravate pure motor chronic inflammatory demyelinating polyneuropathy?","authors":"Norito Kokubun,&nbsp;Kei Funakoshi,&nbsp;Nobuhiro Yuki","doi":"10.1111/jns.12639","DOIUrl":"10.1111/jns.12639","url":null,"abstract":"","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"286-287"},"PeriodicalIF":3.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}