ArticleNature genetics2020
Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 83 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
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83citing papers in PubMed, 1 pooled it
14.0field-weighted citation impact, top 1% of its field
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
- Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a 'treatabolome'.Journal of neuromuscular diseases · 2021Pooled it
- Metabolic reprogramming in diabetic panvascular disease: Molecular mechanism and therapeutic strategies.iScience · 2026Review
- Unexpected Conduction Blocks inClinical case reports · 2026Article
- Longitudinal five-year follow-up by muscle MRI and high-resolution nerve ultrasound in hereditary neuropathies.Neurological research and practice · 2026Article
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.Nature genetics · 2026Article
- Research Trends and Insights of Charcot-Marie-Tooth Disease (CMT): A Visualization Analysis (2000-2025).Health science reports · 2026Article
- Charcot-Marie-Tooth disease and related neuropathies.Nature reviews. Disease primers · 2026Review
- [Identification of SORD as A Key Gene Mediating Osimertinib Primary Resistance in EGFR-Mutant Lung Adenocarcinoma via Machine Learning and Methylomics].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- Genomic signatures of subterranean lifestyle and ecological adaptation in Myospalax.BMC biology · 2025Article
- The continued promise of genomic technologies and software in neurogenetics.Journal of neuromuscular diseases · 2025Review
- Gene-Pseudogene Inversions as a Hidden Source of Missing Heritability.medRxiv : the preprint server for health sciences · 2025Article
- Genotype and phenotype spectrum of Charcot-Marie-Tooth disease due to mutations in SORD.Brain : a journal of neurology · 2025Article
- Dosage-dependent regulation of embryonic diapause by sorbitol dehydrogenase in the silkworm, Bombyx mori.PLoS genetics · 2025Article
- Fructose and glucose from sugary drinks enhance colorectal cancer metastasis via SORD.Nature metabolism · 2025Article
- Identification of genes related to the effects of bicalutamide and zoladex on benign prostatic hyperplasia.Scientific reports · 2025Article
- Clinical and Genetic Reassessment in Patients With Clinically Diagnosed Hereditary Polyneuropathy.European journal of neurology · 2025Article
- Targeted single cell expression profiling identifies integrators of sleep and metabolic state.G3 (Bethesda, Md.) · 2025Article
- Functional assays inGenome research · 2025Review
- Exploration of Neurodegenerative Diseases Using Long-Read Sequencing and Optical Genome Mapping Technologies.Movement disorders : official journal of the Movement Disorder Society · 2025Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
53 authors at 20 institutions in 11 countries.
Andrea Cortese *Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA. andrea.cortese@ucl.ac.uk.ORCID http://orcid.org/0000-0002-2208-5311
Yi Zhu *Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA.
Adriana P Rebelo *Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.ORCID http://orcid.org/0000-0001-5669-7415
Sara NegriIstituiti Clinici Scientifici Maugeri IRCCS, Environmental Research Center, Pavia, Italy.
Steve CourelDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Lisa AbreuDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Chelsea J BaconDepartment of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Yunhong BaiDepartment of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Dana M Bis-BrewerDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Enrico BugiardiniDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Elena BugloDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Matt C DanziDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Shawna M E FeelyDepartment of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Alkyoni Athanasiou-FragkouliDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Nourelhoda A HaridyDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Inherited Neuropathy Consortium
Rosario IsasiDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Alaa KhanDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Matilde LauràDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Stefania MagriUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Menelaos PipisDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Chiara PisciottaUnit of Rare Neurodegenerative and Neurometabolic Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Eric PowellDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Alexander M RossorDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Paola SaveriUnit of Rare Neurodegenerative and Neurometabolic Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Janet E SowdenDepartment of Neurology, University of Rochester, Rochester, NY, USA.
Stefano TozzaDepartment of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy.
Jana VandrovcovaDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Julia DallmanDepartment of Biology, University of Miami, Coral Gables, FL, USA.
Elena GrignaniIstituiti Clinici Scientifici Maugeri IRCCS, Environmental Research Center, Pavia, Italy.
Enrico MarchioniIRCCS Mondino Foundation, Pavia, Italy.
Steven S SchererDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Beisha TangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Zhiqiang LinDepartment of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
Abdullah Al-AjmiDivision of Neurology, Department of Medicine, Al-Jahra Hospital, Al-Jahra, Kuwait.
Rebecca SchüleDepartment of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research, and Center for Neurology, University of Tübingen, Tübingen, Germany.
Matthis SynofzikDepartment of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research, and Center for Neurology, University of Tübingen, Tübingen, Germany.
Thierry MaisonobeDepartment of Neurophysiology, AP-HP, Sorbonne Université, Hôpital Pitié Salpêtrière, Paris, France.
Tanya StojkovicCentre de Référence des Maladies Neuromusculaires Nord/Est/Ile de France, AP-HP, Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France.
Michaela Auer-GrumbachDepartment of Orthopaedics and Traumatology, Medical University of Vienna, Vienna, Austria.
Mohamed A AbdelhamedDepartment of Neurology and Psychiatry, Faculty of Medicine, Assiut University Hospital, Assiut, Egypt.
Sherifa A HamedDepartment of Neurology and Psychiatry, Faculty of Medicine, Assiut University Hospital, Assiut, Egypt.
Ruxu ZhangDepartment of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
Fiore ManganelliDepartment of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy.
Lucio SantoroDepartment of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy.
Franco TaroniUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Davide PareysonUnit of Rare Neurodegenerative and Neurometabolic Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Henry HouldenDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
David N HerrmannDepartment of Neurology, University of Rochester, Rochester, NY, USA.
Mary M ReillyDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Michael E ShyDepartment of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
R Grace ZhaiDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA. gzhai@med.miami.edu.ORCID http://orcid.org/0000-0002-7599-1430
Stephan ZuchnerDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA. szuchner@med.miami.edu.ORCID http://orcid.org/0000-0002-8498-5235
University of Miami · USNational Hospital for Neurology and Neurosurgery · GBUniversity of Iowa · USFondazione IRCCS Istituto Neurologico Carlo Besta · ITJohns Hopkins University · USChildren's Hospital at Westmead · AUCentral South University · CNUniversity of Colorado Hospital · USUniversity of Minnesota · USUniversity of Naples Federico II · ITAssiut University · EGCedars-Sinai Medical Center · USConnecticut Children's Medical Center · USGerman Center for Neurodegenerative Diseases · DEIstituti Clinici Scientifici Maugeri · ITMassachusetts General Hospital · USNemours Children's Clinic · USSorbonne Université · FRStanford University · USUniversity of Rochester · US
Funding
trainingU54NS065712 · NINDS · WAYNE STATE UNIVERSITY · PI SHY, MICHAEL E. · 2009 to 2023
$19.6MGENOME STUDIES IN HEREDITARY SPASTIC PARAPLEGIA - beyond the exomeR01NS072248 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Stephan Zuchner · 2011 to 2026
$9.2MGenomic Studies in Charcot-Marie-Tooth DiseaseR01NS105755 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SHY, MICHAEL E., ZUCHNER, STEPHAN · 2019 to 2023
$3.2MGenomic Studies in Charcot-Marie-Tooth DiseaseR01NS075764 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SHY, MICHAEL E., ZUCHNER, STEPHAN · 2012 to 2016
$3.0MmicroRNA regulation of NMNAT-mediated Neuroprotection against Peripheral Neuropathy and Chronic PainR61AT010408 · NCCIH · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ZHAI, RONG GRACE · 2019 to 2020
$880kFunctional Interaction of GBAS and SLC41A2 in Drosophila models for UDP_755R21GM119018 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ZHAI, RONG GRACE · 2016 to 2019
$675kAustrian Science Fund FWF I 4699Department of HealthMedical Research Council MR/179744Medical Research Council MR/T001712/1NCCIH NIH HHS R61 AT010408NIGMS NIH HHS R21 GM119018NINDS NIH HHS R01 NS072248NINDS NIH HHS R01 NS075764NINDS NIH HHS R01 NS105755NINDS NIH HHS U54 NS065712Wellcome TrustWellcome Trust 110043/Z/15/ZWellcome Trust 204841/Z/16/Z
Abstract
Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes.
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