Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies
Neuropathic pain is a frequent feature of diabetic peripheral neuropathy (DPN) and small fiber neuropathy (SFN). Resolving the genetic architecture of these painful neuropathies will lead to better disease management strategies, counselling and intervention. Our aims were to profile ten sodium chann...
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2023-05-01
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| author | Rowida Almomani Maurice Sopacua Margherita Marchi Milena Ślęczkowska Patrick Lindsey Bianca T. A. de Greef Janneke G. J. Hoeijmakers Erika Salvi Ingemar S. J. Merkies Maryam Ferdousi Rayaz A. Malik Dan Ziegler Kasper W. J. Derks Gidon Boenhof Filippo Martinelli-Boneschi Daniele Cazzato Raffaella Lombardi Sulayman Dib-Hajj Stephen G. Waxman Hubert J. M. Smeets Monique M. Gerrits Catharina G. Faber Giuseppe Lauria on behalf of the PROPANE Study Group |
| author_facet | Rowida Almomani Maurice Sopacua Margherita Marchi Milena Ślęczkowska Patrick Lindsey Bianca T. A. de Greef Janneke G. J. Hoeijmakers Erika Salvi Ingemar S. J. Merkies Maryam Ferdousi Rayaz A. Malik Dan Ziegler Kasper W. J. Derks Gidon Boenhof Filippo Martinelli-Boneschi Daniele Cazzato Raffaella Lombardi Sulayman Dib-Hajj Stephen G. Waxman Hubert J. M. Smeets Monique M. Gerrits Catharina G. Faber Giuseppe Lauria on behalf of the PROPANE Study Group |
| author_sort | Rowida Almomani |
| collection | DOAJ |
| description | Neuropathic pain is a frequent feature of diabetic peripheral neuropathy (DPN) and small fiber neuropathy (SFN). Resolving the genetic architecture of these painful neuropathies will lead to better disease management strategies, counselling and intervention. Our aims were to profile ten sodium channel genes (SCG) expressed in a nociceptive pathway in painful and painless DPN and painful and painless SFN patients, and to provide a perspective for clinicians who assess patients with painful peripheral neuropathy. Between June 2014 and September 2016, 1125 patients with painful-DPN (<i>n</i> = 237), painless-DPN (<i>n</i> = 309), painful-SFN (<i>n</i> = 547) and painless-SFN (<i>n</i> = 32), recruited in four different centers, were analyzed for <i>SCN3A, SCN7A-SCN11A</i> and <i>SCN1B-SCN4B</i> variants by single molecule Molecular inversion probes-Next Generation Sequence. Patients were grouped based on phenotype and the presence of SCG variants. Screening of <i>SCN3A, SCN7A-SCN11A,</i> and <i>SCN1B-SCN4B</i> revealed 125 different (potential) pathogenic variants in 194 patients (17.2%, <i>n</i> = 194/1125). A potential pathogenic variant was present in 18.1% (<i>n</i> = 142/784) of painful neuropathy patients vs. 15.2% (<i>n</i> = 52/341) of painless neuropathy patients (17.3% (<i>n</i> = 41/237) for painful-DPN patients, 14.9% (<i>n</i> = 46/309) for painless-DPN patients, 18.5% (<i>n</i> = 101/547) for painful-SFN patients, and 18.8% (<i>n</i> = 6/32) for painless-SFN patients). Of the variants detected, 70% were in <i>SCN7A, SCN9A, SCN10A</i> and <i>SCN11A</i>. The frequency of <i>SCN9A</i> and <i>SCN11A</i> variants was the highest in painful-SFN patients, <i>SCN7A</i> variants in painful-DPN patients, and <i>SCN10A</i> variants in painless-DPN patients. Our findings suggest that rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification should aid in a better understanding of the genetic variability in patients with painful and painless neuropathy, and may lead to better risk stratification and the development of more targeted and personalized pain treatments. |
| first_indexed | 2024-03-11T04:16:08Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:16:08Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5ee6d87e3e8943d89d2c59bdde7f5eff2023-11-17T23:07:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249827810.3390/ijms24098278Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless NeuropathiesRowida Almomani0Maurice Sopacua1Margherita Marchi2Milena Ślęczkowska3Patrick Lindsey4Bianca T. A. de Greef5Janneke G. J. Hoeijmakers6Erika Salvi7Ingemar S. J. Merkies8Maryam Ferdousi9Rayaz A. Malik10Dan Ziegler11Kasper W. J. Derks12Gidon Boenhof13Filippo Martinelli-Boneschi14Daniele Cazzato15Raffaella Lombardi16Sulayman Dib-Hajj17Stephen G. Waxman18Hubert J. M. Smeets19Monique M. Gerrits20Catharina G. Faber21Giuseppe Lauria22on behalf of the PROPANE Study GroupDepartment of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid 22110, JordanDepartment of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Centre+, 6229 HX Maastricht, The NetherlandsNeuroalgology Unit, IRCCS Foundation “Carlo Besta” Neurological Institute, 20133 Milan, ItalyClinical Genomics Unit, Department of Genetics and Cell Biology, Maastricht University, 6229 ER Maastricht, The NetherlandsClinical Genomics Unit, Department of Genetics and Cell Biology, Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Centre+, 6229 HX Maastricht, The NetherlandsDepartment of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Centre+, 6229 HX Maastricht, The NetherlandsNeuroalgology Unit, IRCCS Foundation “Carlo Besta” Neurological Institute, 20133 Milan, ItalyDepartment of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Centre+, 6229 HX Maastricht, The NetherlandsInstitute of Cardiovascular Sciences, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9P, UKInstitute of Cardiovascular Sciences, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9P, UKGerman Diabetes Centre, 40225 Düsseldorf, GermanyDepartment of Clinical Genetics, Maastricht University Medical Centre+, 6229 HX Maastricht, The NetherlandsInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, 40225 Düsseldorf, GermanyLaboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, ItalyNeuroalgology Unit, IRCCS Foundation “Carlo Besta” Neurological Institute, 20133 Milan, ItalyNeuroalgology Unit, IRCCS Foundation “Carlo Besta” Neurological Institute, 20133 Milan, ItalyDepartment of Neurology, Yale University School of Medicine, New Haven, CT 06510, USADepartment of Neurology, Yale University School of Medicine, New Haven, CT 06510, USAClinical Genomics Unit, Department of Genetics and Cell Biology, Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Clinical Genetics, Maastricht University Medical Centre+, 6229 HX Maastricht, The NetherlandsDepartment of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Centre+, 6229 HX Maastricht, The NetherlandsNeuroalgology Unit, IRCCS Foundation “Carlo Besta” Neurological Institute, 20133 Milan, ItalyNeuropathic pain is a frequent feature of diabetic peripheral neuropathy (DPN) and small fiber neuropathy (SFN). Resolving the genetic architecture of these painful neuropathies will lead to better disease management strategies, counselling and intervention. Our aims were to profile ten sodium channel genes (SCG) expressed in a nociceptive pathway in painful and painless DPN and painful and painless SFN patients, and to provide a perspective for clinicians who assess patients with painful peripheral neuropathy. Between June 2014 and September 2016, 1125 patients with painful-DPN (<i>n</i> = 237), painless-DPN (<i>n</i> = 309), painful-SFN (<i>n</i> = 547) and painless-SFN (<i>n</i> = 32), recruited in four different centers, were analyzed for <i>SCN3A, SCN7A-SCN11A</i> and <i>SCN1B-SCN4B</i> variants by single molecule Molecular inversion probes-Next Generation Sequence. Patients were grouped based on phenotype and the presence of SCG variants. Screening of <i>SCN3A, SCN7A-SCN11A,</i> and <i>SCN1B-SCN4B</i> revealed 125 different (potential) pathogenic variants in 194 patients (17.2%, <i>n</i> = 194/1125). A potential pathogenic variant was present in 18.1% (<i>n</i> = 142/784) of painful neuropathy patients vs. 15.2% (<i>n</i> = 52/341) of painless neuropathy patients (17.3% (<i>n</i> = 41/237) for painful-DPN patients, 14.9% (<i>n</i> = 46/309) for painless-DPN patients, 18.5% (<i>n</i> = 101/547) for painful-SFN patients, and 18.8% (<i>n</i> = 6/32) for painless-SFN patients). Of the variants detected, 70% were in <i>SCN7A, SCN9A, SCN10A</i> and <i>SCN11A</i>. The frequency of <i>SCN9A</i> and <i>SCN11A</i> variants was the highest in painful-SFN patients, <i>SCN7A</i> variants in painful-DPN patients, and <i>SCN10A</i> variants in painless-DPN patients. Our findings suggest that rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification should aid in a better understanding of the genetic variability in patients with painful and painless neuropathy, and may lead to better risk stratification and the development of more targeted and personalized pain treatments.https://www.mdpi.com/1422-0067/24/9/8278diabetic neuropathysmall fiber neuropathyneuropathic painmolecular inversion probesnext generation sequencingsodium channel genes variants |
| spellingShingle | Rowida Almomani Maurice Sopacua Margherita Marchi Milena Ślęczkowska Patrick Lindsey Bianca T. A. de Greef Janneke G. J. Hoeijmakers Erika Salvi Ingemar S. J. Merkies Maryam Ferdousi Rayaz A. Malik Dan Ziegler Kasper W. J. Derks Gidon Boenhof Filippo Martinelli-Boneschi Daniele Cazzato Raffaella Lombardi Sulayman Dib-Hajj Stephen G. Waxman Hubert J. M. Smeets Monique M. Gerrits Catharina G. Faber Giuseppe Lauria on behalf of the PROPANE Study Group Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies International Journal of Molecular Sciences diabetic neuropathy small fiber neuropathy neuropathic pain molecular inversion probes next generation sequencing sodium channel genes variants |
| title | Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies |
| title_full | Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies |
| title_fullStr | Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies |
| title_full_unstemmed | Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies |
| title_short | Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies |
| title_sort | genetic profiling of sodium channels in diabetic painful and painless and idiopathic painful and painless neuropathies |
| topic | diabetic neuropathy small fiber neuropathy neuropathic pain molecular inversion probes next generation sequencing sodium channel genes variants |
| url | https://www.mdpi.com/1422-0067/24/9/8278 |
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