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Disease ID:333
Associated with:1 target
Primary erythermalgia | Sodium channelopathy-related small fiber neuropathy
Database Links
OMIM: 133020
Orphanet: ORPHA1956, ORPHA90026, ORPHA306577


Role:  Nav1.7 mutations cause burning pain and flushing of the extremities.
References:  6,8,10-11,25-27
Mutations:  Nav1.7 is associated with 28 mutation. Click here for details


No ligand related data available for Erythermalgia


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1. Ahn HS, Dib-Hajj SD, Cox JJ, Tyrrell L, Elmslie FV, Clarke AA, Drenth JP, Woods CG, Waxman SG. (2010) A new Nav1.7 sodium channel mutation I234T in a child with severe pain. Eur J Pain, 14 (9): 944-50. [PMID:20385509]

2. Cheng X, Dib-Hajj SD, Tyrrell L, Te Morsche RH, Drenth JP, Waxman SG. (2011) Deletion mutation of sodium channel Na(V)1.7 in inherited erythromelalgia: enhanced slow inactivation modulates dorsal root ganglion neuron hyperexcitability. Brain, 134 (Pt 7): 1972-86. [PMID:21705421]

3. Cheng X, Dib-Hajj SD, Tyrrell L, Waxman SG. (2008) Mutation I136V alters electrophysiological properties of the Na(v)1.7 channel in a family with onset of erythromelalgia in the second decade. Mol Pain, 4: 1. [PMID:18171466]

4. Cheng X, Dib-Hajj SD, Tyrrell L, Wright DA, Fischer TZ, Waxman SG. (2010) Mutations at opposite ends of the DIII/S4-S5 linker of sodium channel Na V 1.7 produce distinct pain disorders. Mol Pain, 6: 24. [PMID:20429905]

5. Choi JS, Cheng X, Foster E, Leffler A, Tyrrell L, Te Morsche RH, Eastman EM, Jansen HJ, Huehne K, Nau C et al.. (2010) Alternative splicing may contribute to time-dependent manifestation of inherited erythromelalgia. Brain, 133 (Pt 6): 1823-35. [PMID:20478850]

6. Choi JS, Dib-Hajj SD, Waxman SG. (2006) Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy. Neurology, 67 (9): 1563-7. [PMID:16988069]

7. Choi JS, Zhang L, Dib-Hajj SD, Han C, Tyrrell L, Lin Z, Wang X, Yang Y, Waxman SG. (2009) Mexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use-dependent current fall-off. Exp. Neurol., 216 (2): 383-9. [PMID:19162012]

8. Coulter DA, Rafiq A, Shumate M, Gong QZ, DeLorenzo RJ, Lyeth BG. (1996) Brain injury-induced enhanced limbic epileptogenesis: anatomical and physiological parallels to an animal model of temporal lobe epilepsy. Epilepsy Res., 26 (1): 81-91. [PMID:8985690]

9. Cummins TR, Dib-Hajj SD, Waxman SG. (2004) Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. J. Neurosci., 24 (38): 8232-6. [PMID:15385606]

10. Dib-Hajj SD, Cummins TR, Black JA, Waxman SG. (2010) Sodium channels in normal and pathological pain. Annu. Rev. Neurosci., 33: 325-47. [PMID:20367448]

11. Dib-Hajj SD, Rush AM, Cummins TR, Hisama FM, Novella S, Tyrrell L, Marshall L, Waxman SG. (2005) Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain, 128 (Pt 8): 1847-54. [PMID:15958509]

12. Drenth JP, te Morsche RH, Guillet G, Taieb A, Kirby RL, Jansen JB. (2005) SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels. J. Invest. Dermatol., 124 (6): 1333-8. [PMID:15955112]

13. Estacion M, Choi JS, Eastman EM, Lin Z, Li Y, Tyrrell L, Yang Y, Dib-Hajj SD, Waxman SG. (2010) Can robots patch-clamp as well as humans? Characterization of a novel sodium channel mutation. J. Physiol. (Lond.), 588 (Pt 11): 1915-27. [PMID:20123784]

14. Estacion M, Dib-Hajj SD, Benke PJ, Te Morsche RH, Eastman EM, Macala LJ, Drenth JP, Waxman SG. (2008) NaV1.7 gain-of-function mutations as a continuum: A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. J. Neurosci., 28 (43): 11079-88. [PMID:18945915]

15. Estacion M, Han C, Choi JS, Hoeijmakers JG, Lauria G, Drenth JP, Gerrits MM, Dib-Hajj SD, Faber CG, Merkies IS et al.. (2011) Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of NaV1.7. Mol Pain, 7: 92. [PMID:22136189]

16. Faber CG, Hoeijmakers JG, Ahn HS, Cheng X, Han C, Choi JS, Estacion M, Lauria G, Vanhoutte EK, Gerrits MM et al.. (2012) Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. Ann. Neurol., 71 (1): 26-39. [PMID:21698661]

17. Fischer TZ, Gilmore ES, Estacion M, Eastman E, Taylor S, Melanson M, Dib-Hajj SD, Waxman SG. (2009) A novel Nav1.7 mutation producing carbamazepine-responsive erythromelalgia. Ann. Neurol., 65 (6): 733-41. [PMID:19557861]

18. Han C, Dib-Hajj SD, Lin Z, Li Y, Eastman EM, Tyrrell L, Cao X, Yang Y, Waxman SG. (2009) Early- and late-onset inherited erythromelalgia: genotype-phenotype correlation. Brain, 132 (Pt 7): 1711-22. [PMID:19369487]

19. Han C, Hoeijmakers JG, Ahn HS, Zhao P, Shah P, Lauria G, Gerrits MM, te Morsche RH, Dib-Hajj SD, Drenth JP et al.. (2012) Nav1.7-related small fiber neuropathy: impaired slow-inactivation and DRG neuron hyperexcitability. Neurology, 78 (21): 1635-43. [PMID:22539570]

20. Han C, Hoeijmakers JG, Liu S, Gerrits MM, te Morsche RH, Lauria G, Dib-Hajj SD, Drenth JP, Faber CG, Merkies IS et al.. (2012) Functional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy. Brain, 135 (Pt 9): 2613-28. [PMID:22826602]

21. Han C, Rush AM, Dib-Hajj SD, Li S, Xu Z, Wang Y, Tyrrell L, Wang X, Yang Y, Waxman SG. (2006) Sporadic onset of erythermalgia: a gain-of-function mutation in Nav1.7. Ann. Neurol., 59 (3): 553-8. [PMID:16392115]

22. Harty TP, Dib-Hajj SD, Tyrrell L, Blackman R, Hisama FM, Rose JB, Waxman SG. (2006) Na(V)1.7 mutant A863P in erythromelalgia: effects of altered activation and steady-state inactivation on excitability of nociceptive dorsal root ganglion neurons. J. Neurosci., 26 (48): 12566-75. [PMID:17135418]

23. Lampert A, Dib-Hajj SD, Eastman EM, Tyrrell L, Lin Z, Yang Y, Waxman SG. (2009) Erythromelalgia mutation L823R shifts activation and inactivation of threshold sodium channel Nav1.7 to hyperpolarized potentials. Biochem. Biophys. Res. Commun., 390 (2): 319-24. [PMID:19800314]

24. Lampert A, Dib-Hajj SD, Tyrrell L, Waxman SG. (2006) Size matters: Erythromelalgia mutation S241T in Nav1.7 alters channel gating. J. Biol. Chem., 281 (47): 36029-35. [PMID:17008310]

25. Michiels JJ, te Morsche RH, Jansen JB, Drenth JP. (2005) Autosomal dominant erythermalgia associated with a novel mutation in the voltage-gated sodium channel alpha subunit Nav1.7. Arch. Neurol., 62 (10): 1587-90. [PMID:16216943]

26. Waxman SG, Dib-Hajj S. (2005) Erythermalgia: molecular basis for an inherited pain syndrome. Trends Mol Med, 11 (12): 555-62. [PMID:16278094]

27. Yang Y, Wang Y, Li S, Xu Z, Li H, Ma L, Fan J, Bu D, Liu B, Fan Z et al.. (2004) Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J. Med. Genet., 41 (3): 171-4. [PMID:14985375]