Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of Na<sub<V</sub<1.7
<p<Abstract</p< <p<Background</p< <p<Sodium channel Na<sub<V</sub<1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplif...
Ausführliche Beschreibung
Autor*in: |
Estacion Mark [verfasserIn] Han Chongyang [verfasserIn] Choi Jin-Sung [verfasserIn] Hoeijmakers Janneke GJ [verfasserIn] Lauria Giuseppe [verfasserIn] Drenth Joost PH [verfasserIn] Gerrits Monique M [verfasserIn] Dib-Hajj Sulayman D [verfasserIn] Faber Catharina G [verfasserIn] Merkies Ingemar SJ [verfasserIn] Waxman Stephen G [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2011 |
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Übergeordnetes Werk: |
In: Molecular Pain - SAGE Publishing, 2005, 7(2011), 1, p 92 |
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Übergeordnetes Werk: |
volume:7 ; year:2011 ; number:1, p 92 |
Links: |
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DOI / URN: |
10.1186/1744-8069-7-92 |
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Katalog-ID: |
DOAJ078293707 |
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245 | 1 | 0 | |a Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of Na<sub<V</sub<1.7 |
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520 | |a <p<Abstract</p< <p<Background</p< <p<Sodium channel Na<sub<V</sub<1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na<sub<V</sub<1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na<sub<V</sub<1.7/I228M variant.</p< <p<Methods</p< <p<We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na<sub<V</sub<1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p< <p<Results</p< <p<We report three different clinical presentations of the I228M Na<sub<V</sub<1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na<sub<V</sub<1.7 variant, two of which are from a single family. We also demonstrate that the Na<sub<V</sub<1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p< <p<Conclusion</p< <p<Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na<sub<V</sub<1.7.</p< | ||
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10.1186/1744-8069-7-92 doi (DE-627)DOAJ078293707 (DE-599)DOAJe177c716b7ab4c698cf34336fb513beb DE-627 ger DE-627 rakwb eng RB1-214 Estacion Mark verfasserin aut Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of Na<sub<V</sub<1.7 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Sodium channel Na<sub<V</sub<1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na<sub<V</sub<1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na<sub<V</sub<1.7/I228M variant.</p< <p<Methods</p< <p<We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na<sub<V</sub<1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p< <p<Results</p< <p<We report three different clinical presentations of the I228M Na<sub<V</sub<1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na<sub<V</sub<1.7 variant, two of which are from a single family. We also demonstrate that the Na<sub<V</sub<1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p< <p<Conclusion</p< <p<Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na<sub<V</sub<1.7.</p< Pathology Han Chongyang verfasserin aut Choi Jin-Sung verfasserin aut Hoeijmakers Janneke GJ verfasserin aut Lauria Giuseppe verfasserin aut Drenth Joost PH verfasserin aut Gerrits Monique M verfasserin aut Dib-Hajj Sulayman D verfasserin aut Faber Catharina G verfasserin aut Merkies Ingemar SJ verfasserin aut Waxman Stephen G verfasserin aut In Molecular Pain SAGE Publishing, 2005 7(2011), 1, p 92 (DE-627)47753368X (DE-600)2174252-2 17448069 nnns volume:7 year:2011 number:1, p 92 https://doi.org/10.1186/1744-8069-7-92 kostenfrei https://doaj.org/article/e177c716b7ab4c698cf34336fb513beb kostenfrei http://www.molecularpain.com/content/7/1/92 kostenfrei https://doaj.org/toc/1744-8069 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2011 1, p 92 |
spelling |
10.1186/1744-8069-7-92 doi (DE-627)DOAJ078293707 (DE-599)DOAJe177c716b7ab4c698cf34336fb513beb DE-627 ger DE-627 rakwb eng RB1-214 Estacion Mark verfasserin aut Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of Na<sub<V</sub<1.7 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Sodium channel Na<sub<V</sub<1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na<sub<V</sub<1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na<sub<V</sub<1.7/I228M variant.</p< <p<Methods</p< <p<We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na<sub<V</sub<1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p< <p<Results</p< <p<We report three different clinical presentations of the I228M Na<sub<V</sub<1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na<sub<V</sub<1.7 variant, two of which are from a single family. We also demonstrate that the Na<sub<V</sub<1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p< <p<Conclusion</p< <p<Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na<sub<V</sub<1.7.</p< Pathology Han Chongyang verfasserin aut Choi Jin-Sung verfasserin aut Hoeijmakers Janneke GJ verfasserin aut Lauria Giuseppe verfasserin aut Drenth Joost PH verfasserin aut Gerrits Monique M verfasserin aut Dib-Hajj Sulayman D verfasserin aut Faber Catharina G verfasserin aut Merkies Ingemar SJ verfasserin aut Waxman Stephen G verfasserin aut In Molecular Pain SAGE Publishing, 2005 7(2011), 1, p 92 (DE-627)47753368X (DE-600)2174252-2 17448069 nnns volume:7 year:2011 number:1, p 92 https://doi.org/10.1186/1744-8069-7-92 kostenfrei https://doaj.org/article/e177c716b7ab4c698cf34336fb513beb kostenfrei http://www.molecularpain.com/content/7/1/92 kostenfrei https://doaj.org/toc/1744-8069 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2011 1, p 92 |
allfields_unstemmed |
10.1186/1744-8069-7-92 doi (DE-627)DOAJ078293707 (DE-599)DOAJe177c716b7ab4c698cf34336fb513beb DE-627 ger DE-627 rakwb eng RB1-214 Estacion Mark verfasserin aut Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of Na<sub<V</sub<1.7 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Sodium channel Na<sub<V</sub<1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na<sub<V</sub<1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na<sub<V</sub<1.7/I228M variant.</p< <p<Methods</p< <p<We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na<sub<V</sub<1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p< <p<Results</p< <p<We report three different clinical presentations of the I228M Na<sub<V</sub<1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na<sub<V</sub<1.7 variant, two of which are from a single family. We also demonstrate that the Na<sub<V</sub<1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p< <p<Conclusion</p< <p<Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na<sub<V</sub<1.7.</p< Pathology Han Chongyang verfasserin aut Choi Jin-Sung verfasserin aut Hoeijmakers Janneke GJ verfasserin aut Lauria Giuseppe verfasserin aut Drenth Joost PH verfasserin aut Gerrits Monique M verfasserin aut Dib-Hajj Sulayman D verfasserin aut Faber Catharina G verfasserin aut Merkies Ingemar SJ verfasserin aut Waxman Stephen G verfasserin aut In Molecular Pain SAGE Publishing, 2005 7(2011), 1, p 92 (DE-627)47753368X (DE-600)2174252-2 17448069 nnns volume:7 year:2011 number:1, p 92 https://doi.org/10.1186/1744-8069-7-92 kostenfrei https://doaj.org/article/e177c716b7ab4c698cf34336fb513beb kostenfrei http://www.molecularpain.com/content/7/1/92 kostenfrei https://doaj.org/toc/1744-8069 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2011 1, p 92 |
allfieldsGer |
10.1186/1744-8069-7-92 doi (DE-627)DOAJ078293707 (DE-599)DOAJe177c716b7ab4c698cf34336fb513beb DE-627 ger DE-627 rakwb eng RB1-214 Estacion Mark verfasserin aut Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of Na<sub<V</sub<1.7 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Sodium channel Na<sub<V</sub<1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na<sub<V</sub<1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na<sub<V</sub<1.7/I228M variant.</p< <p<Methods</p< <p<We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na<sub<V</sub<1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p< <p<Results</p< <p<We report three different clinical presentations of the I228M Na<sub<V</sub<1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na<sub<V</sub<1.7 variant, two of which are from a single family. We also demonstrate that the Na<sub<V</sub<1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p< <p<Conclusion</p< <p<Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na<sub<V</sub<1.7.</p< Pathology Han Chongyang verfasserin aut Choi Jin-Sung verfasserin aut Hoeijmakers Janneke GJ verfasserin aut Lauria Giuseppe verfasserin aut Drenth Joost PH verfasserin aut Gerrits Monique M verfasserin aut Dib-Hajj Sulayman D verfasserin aut Faber Catharina G verfasserin aut Merkies Ingemar SJ verfasserin aut Waxman Stephen G verfasserin aut In Molecular Pain SAGE Publishing, 2005 7(2011), 1, p 92 (DE-627)47753368X (DE-600)2174252-2 17448069 nnns volume:7 year:2011 number:1, p 92 https://doi.org/10.1186/1744-8069-7-92 kostenfrei https://doaj.org/article/e177c716b7ab4c698cf34336fb513beb kostenfrei http://www.molecularpain.com/content/7/1/92 kostenfrei https://doaj.org/toc/1744-8069 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2011 1, p 92 |
allfieldsSound |
10.1186/1744-8069-7-92 doi (DE-627)DOAJ078293707 (DE-599)DOAJe177c716b7ab4c698cf34336fb513beb DE-627 ger DE-627 rakwb eng RB1-214 Estacion Mark verfasserin aut Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of Na<sub<V</sub<1.7 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Sodium channel Na<sub<V</sub<1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na<sub<V</sub<1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na<sub<V</sub<1.7/I228M variant.</p< <p<Methods</p< <p<We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na<sub<V</sub<1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p< <p<Results</p< <p<We report three different clinical presentations of the I228M Na<sub<V</sub<1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na<sub<V</sub<1.7 variant, two of which are from a single family. We also demonstrate that the Na<sub<V</sub<1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p< <p<Conclusion</p< <p<Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na<sub<V</sub<1.7.</p< Pathology Han Chongyang verfasserin aut Choi Jin-Sung verfasserin aut Hoeijmakers Janneke GJ verfasserin aut Lauria Giuseppe verfasserin aut Drenth Joost PH verfasserin aut Gerrits Monique M verfasserin aut Dib-Hajj Sulayman D verfasserin aut Faber Catharina G verfasserin aut Merkies Ingemar SJ verfasserin aut Waxman Stephen G verfasserin aut In Molecular Pain SAGE Publishing, 2005 7(2011), 1, p 92 (DE-627)47753368X (DE-600)2174252-2 17448069 nnns volume:7 year:2011 number:1, p 92 https://doi.org/10.1186/1744-8069-7-92 kostenfrei https://doaj.org/article/e177c716b7ab4c698cf34336fb513beb kostenfrei http://www.molecularpain.com/content/7/1/92 kostenfrei https://doaj.org/toc/1744-8069 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2011 1, p 92 |
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Estacion Mark @@aut@@ Han Chongyang @@aut@@ Choi Jin-Sung @@aut@@ Hoeijmakers Janneke GJ @@aut@@ Lauria Giuseppe @@aut@@ Drenth Joost PH @@aut@@ Gerrits Monique M @@aut@@ Dib-Hajj Sulayman D @@aut@@ Faber Catharina G @@aut@@ Merkies Ingemar SJ @@aut@@ Waxman Stephen G @@aut@@ |
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intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of na<sub<v</sub<1.7 |
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Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of Na<sub<V</sub<1.7 |
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<p<Abstract</p< <p<Background</p< <p<Sodium channel Na<sub<V</sub<1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na<sub<V</sub<1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na<sub<V</sub<1.7/I228M variant.</p< <p<Methods</p< <p<We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na<sub<V</sub<1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p< <p<Results</p< <p<We report three different clinical presentations of the I228M Na<sub<V</sub<1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na<sub<V</sub<1.7 variant, two of which are from a single family. We also demonstrate that the Na<sub<V</sub<1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p< <p<Conclusion</p< <p<Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na<sub<V</sub<1.7.</p< |
abstractGer |
<p<Abstract</p< <p<Background</p< <p<Sodium channel Na<sub<V</sub<1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na<sub<V</sub<1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na<sub<V</sub<1.7/I228M variant.</p< <p<Methods</p< <p<We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na<sub<V</sub<1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p< <p<Results</p< <p<We report three different clinical presentations of the I228M Na<sub<V</sub<1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na<sub<V</sub<1.7 variant, two of which are from a single family. We also demonstrate that the Na<sub<V</sub<1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p< <p<Conclusion</p< <p<Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na<sub<V</sub<1.7.</p< |
abstract_unstemmed |
<p<Abstract</p< <p<Background</p< <p<Sodium channel Na<sub<V</sub<1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na<sub<V</sub<1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na<sub<V</sub<1.7/I228M variant.</p< <p<Methods</p< <p<We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na<sub<V</sub<1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p< <p<Results</p< <p<We report three different clinical presentations of the I228M Na<sub<V</sub<1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na<sub<V</sub<1.7 variant, two of which are from a single family. We also demonstrate that the Na<sub<V</sub<1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p< <p<Conclusion</p< <p<Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na<sub<V</sub<1.7.</p< |
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