دورية أكاديمية
Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort
| العنوان: | Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort |
|---|---|
| المؤلفون: | Themistocleous, Andreas C, Baskozos, Georgios, Blesneac, Iulia, Comini, Maddalena, Megy, Karyn, Chong, Sam, Deevi, Sri VV, Ginsberg, Lionel, Gosal, David, Hadden, Robert DM, Horvath, Rita, Mahdi-Rogers, Mohamed, Manzur, Adnan, Mapeta, Rutendo, Marshall, Andrew, Matthews, Emma, McCarthy, Mark I, Reilly, Mary M, Renton, Tara, Rice, Andrew SC, Vale, Tom A, van Zuydam, Natalie, Walker, Suellen M, Woods, Christopher Geoffrey, Bennett, David LH |
| المصدر: | Brain Commun , 5 (2) , Article fcad037. (2023) |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | neuropathic pain, peripheral neuropathy, sodium channels, whole genome sequencing |
| الوصف: | The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical presentation. Patients with extreme neuropathic pain phenotypes (both sensory loss and gain) were recruited from secondary care clinics in the UK and underwent whole genome sequencing as part of the National Institute for Health and Care Research Bioresource Rare Diseases project. A multidisciplinary team assessed the pathogenicity of rare variants in genes previously known to cause neuropathic pain disorders and exploratory analysis of research candidate genes was completed. Association testing for genes carrying rare variants was completed using the gene-wise approach of the combined burden and variance-component test SKAT-O. Patch clamp analysis was performed on transfected HEK293T cells for research candidate variants of genes encoding ion channels. The results include the following: (i) Medically actionable variants were found in 12% of study participants (205 recruited), including known pathogenic variants: SCN9A(ENST00000409672.1): c.2544T>C, p.Ile848Thr that causes inherited erythromelalgia, and SPTLC1(ENST00000262554.2):c.340T>G, p.Cys133Tr variant that causes hereditary sensory neuropathy type-1. (ii) Clinically relevant variants were most common in voltage-gated sodium channels (Nav). (iii) SCN9A(ENST00000409672.1):c.554G>A, pArg185His variant was more common in non-freezing cold injury participants than controls and causes a gain of function of NaV1.7 after cooling (the environmental trigger for non-freezing cold injury). (iv) Rare variant association testing showed a significant difference in distribution for genes NGF, KIF1A, SCN8A, TRPM8, KIF1A, TRPA1 and the regulatory regions of genes SCN11A, FLVCR1, KIF1A and SCN9A between European participants with neuropathic pain and controls. (v) The ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10166688/1/Investigating%20genotype-phenotype%20relationship%20of%20extreme%20neuropathic%20pain%20disorders%20in%20a%20UK%20national%20cohort.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10166688Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10166688/1/Investigating%20genotype-phenotype%20relationship%20of%20extreme%20neuropathic%20pain%20disorders%20in%20a%20UK%20national%20cohort.pdfTest https://discovery.ucl.ac.uk/id/eprint/10166688Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.FD25B0FA |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |