ArticleAmerican journal of human genetics2014
Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2.
Registry-linked trialOpen access · hybridAbstract readCase Reports
In one paragraph
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05152823 (Phase I/IIa Intrathecal Gene Delivery Clinical Trial for IGHMBP2-Related Diseases), which is not on this map. Cited by 60 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
NCT05152823 phase1 / phase2enrolling by invitationnot on this mapstarted 2021, after this paper: background citation
Phase I/IIa Intrathecal Gene Delivery Clinical Trial for IGHMBP2-Related Diseases
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Exploring the relationship betweenFrontiers in neuroscience · 2023Pooled it
- A class of deep intronicmedRxiv : the preprint server for health sciences · 2026Article
- AAV9 gene therapy optimization for SMARD1/CMT2S: safety and long-term efficacy comparison of two vectors in a SMARD1 preclinical model.Journal of biomedical science · 2026Article
- [Generation of induced pluripotent stem cells from peripheral blood mononuclear cells of a patient with autosomal recessive CharcotZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- The Ighmbp2-R604X mouse presents with the most severe SMARD1 clinical symptoms resulting in failure to thrive, respiratory and feeding deficits, aspiration and severe axon and muscle pathology.Neurobiology of disease · 2025Article
- SARM1 Inhibition in Three Mouse Models of Charcot-Marie-Tooth Disease.Journal of the peripheral nervous system : JPNS · 2025Article
- A cross-sectional survey on the health status of patients with Charcot-Marie-Tooth disease in a Chinese national patient group.Journal of neurology · 2025Article
- Potential ASO-based personalized treatment for Charcot-Marie-Tooth disease type 2S.Molecular therapy. Nucleic acids · 2025Article
- Activators of the 26S proteasome when protein degradation increases.Experimental & molecular medicine · 2025Review
- Ighmbp2 mutations and disease pathology: Defining differences that differentiate SMARD1 and CMT2S.Experimental neurology · 2025Article
- The clinical and genetic profiles of spinal muscular atrophy with respiratory distress type 1 and identification of a novel mutation inFrontiers in genetics · 2025Article
- Noncoding variants are a rare cause of recessive developmental disorders in trans with coding variants.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Expanding the genetic spectrum of hereditary motor sensory neuropathies in Pakistan.BMC neurology · 2024Article
- Clinically relevant mouse models of severe spinal muscular atrophy with respiratory distress type 1.Human molecular genetics · 2024Article
- Clinical and Genetic Profiles of 5q- and Non-5q-Spinal Muscular Atrophy Diseases in Pediatric Patients.Genes · 2024Review
- IGHMBP2 deletion suppresses translation and activates the integrated stress response.Life science alliance · 2024Article
- Article
- Disease Mechanisms and Therapeutic Approaches in SMARD1-Insights from Animal Models and Cell Models.Biomedicines · 2024Review
- The contribution and therapeutic implications of IGHMBP2 mutations on IGHMBP2 biochemical activity and ABT1 association.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Case report: Heterozygous variation in the IGHMBP2 gene leading to spinal muscular atrophy with respiratory distress type 1.Frontiers in neurology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
40 authors at 19 institutions in 10 countries.
Ellen CottenieMRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Department of Molecular Neurosciences, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Andrzej KochanskiNeuromuscular Unit, Mossakowski Medical Research Centre Polish Academy of Sciences, Centre of Biostructure, Medical University of Warsaw, Pawinskiego 5, 02-106 Warsaw, Poland.
Albena JordanovaVIB Department of Molecular Genetics, University of Antwerp, Antwerpen 2610, Belgium.
Boglarka BansagiInstitute of Genetic Medicine, MRC Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Magdalena ZimonVIB Department of Molecular Genetics, University of Antwerp, Antwerpen 2610, Belgium.
Alejandro HorgaMRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Department of Molecular Neurosciences, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Zane JaunmuktaneDivision of Neuropathology and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Paola SaveriClinic of Central and Peripheral Degenerative Neuropathies Unit, IRCCS Foundation, C. Besta Neurological Institute, Via Celoria 11, 20133 Milan, Italy.
Vedrana Milic RasicClinic for Neurology and Psychiatry for Children and Youth, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Jonathan BaetsVIB Department of Molecular Genetics, University of Antwerp, Antwerpen 2610, Belgium; Laboratory of Neurogenetics, University of Antwerp, Antwerpen 2610, Belgium; Department of Neurology, Antwerp University Hospital, Antwerpen, Belgium.
Marina BartsakouliaInstitute of Genetic Medicine, MRC Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Rafal PloskiDepartment of Medical Genetics, Centre of Biostructure, Medical University of Warsaw, Pawinskiego 5, 02-106 Warsaw, Poland.
Pawel TeteryczDepartment of Medical Genetics, Centre of Biostructure, Medical University of Warsaw, Pawinskiego 5, 02-106 Warsaw, Poland.
Milos NikolicUniversity of Belgrade, Faculty of Medicine, 11000 Belgrade, Serbia.
Ros QuinlivanMRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Matilde LauraMRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Department of Molecular Neurosciences, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Mary G SweeneyNeurogenetics Laboratory, The National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Franco TaroniUnit of Genetics of Neurodegenerative and Metabolic Disease IRCCS Foundation, C. Besta Neurological Institute, Via Celoria 11, 20133 Milan, Italy.
Michael P LunnMRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Isabella MoroniChild Neurology Unit, IRCCS Foundation, C. Besta Neurological Institute, Via Celoria 11, 20133 Milan, Italy.
Michael GonzalezJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL 33136, USA.
Michael G HannaMRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Department of Molecular Neurosciences, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Conceicao BettencourtDepartment of Molecular Neurosciences, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Elodie ChabrolDepartment of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Andre FrankeChristian-Albrechts-University, 24118 Kiel, Germany.
Katja von AuSPZ Pediatric Neurology, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Markus SchilhabelChristian-Albrechts-University, 24118 Kiel, Germany.
Dagmara KabzińskaNeuromuscular Unit, Mossakowski Medical Research Centre Polish Academy of Sciences, Centre of Biostructure, Medical University of Warsaw, Pawinskiego 5, 02-106 Warsaw, Poland.
Irena Hausmanowa-PetrusewiczNeuromuscular Unit, Mossakowski Medical Research Centre Polish Academy of Sciences, Centre of Biostructure, Medical University of Warsaw, Pawinskiego 5, 02-106 Warsaw, Poland.
Sebastian BrandnerDivision of Neuropathology and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Siew Choo LimInstitute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673.
Haiwei SongInstitute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673; Life Sciences Institute, Zhejiang University, Hangzhou 310058, People's Republic of China.
Byung-Ok ChoiDepartment of Neurology, Sungkyunkwan University School of Medicine, Seoul 137-710, Korea.
Rita HorvathInstitute of Genetic Medicine, MRC Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Ki-Wha ChungDepartment of Biological Science, Kongju National University, Chungnam 134-701, Korea.
Stephan ZuchnerJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL 33136, USA.
Davide PareysonClinic of Central and Peripheral Degenerative Neuropathies Unit, IRCCS Foundation, C. Besta Neurological Institute, Via Celoria 11, 20133 Milan, Italy.
Matthew HarmsDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Mary M ReillyMRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Department of Molecular Neurosciences, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Henry HouldenMRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Department of Molecular Neurosciences, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Neurogenetics Laboratory, The National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. Electronic address: h.houlden@ucl.ac.uk.
National Hospital for Neurology and Neurosurgery · GBUniversity College London · GBFondazione IRCCS Istituto Neurologico Carlo Besta · ITNewcastle University · GBDr. John T. Macdonald Foundation · USKiel University · DEMedical University of Warsaw · PLPolish Academy of Sciences · PLUniversity of Antwerp · BEAntwerp University Hospital · BECharité - Universitätsmedizin Berlin · DEInstitute of Molecular and Cell Biology · SGKongju National University · KRMossakowski Medical Research Institute, Polish Academy of Sciences · PLSungkyunkwan University · KRUniversity Children's Hospital, Belgrade · RSUniversity of Belgrade · RSWashington University in St. Louis · USZhejiang University · CN
Funding
trainingU54NS065712 · NINDS · WAYNE STATE UNIVERSITY · PI SHY, MICHAEL E. · 2009 to 2023
$19.6MGenomic Studies in Charcot-Marie-Tooth DiseaseR01NS075764 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SHY, MICHAEL E., ZUCHNER, STEPHAN · 2012 to 2016
$3.0MEuropean Research Council 309548Medical Research Council G0601943Medical Research Council G0802760Medical Research Council G1001253Medical Research Council G108/638Medical Research Council MR/J004758/1Medical Research Council MR/K000608/1NINDS NIH HHS R01 NS075764NINDS NIH HHS R01NS075764NINDS NIH HHS U54 NS065712NINDS NIH HHS U54NS065712Wellcome Trust 096919
Abstract
Using a combination of exome sequencing and linkage analysis, we investigated an English family with two affected siblings in their 40s with recessive Charcot-Marie Tooth disease type 2 (CMT2). Compound heterozygous mutations in the immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) gene were identified. Further sequencing revealed a total of 11 CMT2 families with recessively inherited IGHMBP2 gene mutations. IGHMBP2 mutations usually lead to spinal muscular atrophy with respiratory distress type 1 (SMARD1), where most infants die before 1 year of age. The individuals with CMT2 described here, have slowly progressive weakness, wasting and sensory loss, with an axonal neuropathy typical of CMT2, but no significant respiratory compromise. Segregating IGHMBP2 mutations in CMT2 were mainly loss-of-function nonsense in the 5' region of the gene in combination with a truncating frameshift, missense, or homozygous frameshift mutations in the last exon. Mutations in CMT2 were predicted to be less aggressive as compared to those in SMARD1, and fibroblast and lymphoblast studies indicate that the IGHMBP2 protein levels are significantly higher in CMT2 than SMARD1, but lower than controls, suggesting that the clinical phenotype differences are related to the IGHMBP2 protein levels.
Indexed as
Models, MolecularPhenotypeAdultBase SequenceCharcot-Marie-Tooth DiseaseChromosome MappingExomeFemaleHaplotypesHumansMolecular Sequence DataMutation, MissensePedigreeProtein Interaction MappingSequence Analysis, DNASural Nerve
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Registered trials
NCT05152823ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.