Genetic Neurological Channelopathies: Molecular Genetics and Clinical Phenotypes

Overview

Journal J Neurol Neurosurg Psychiatry

Publisher BMJ Publishing Group

Specialties Neurology
Neurosurgery
Psychiatry

Date 2015 Nov 13

PMID 26558925

Citations 48

Authors

J Spillane

D M Kullmann

M G Hanna

Affiliations

Soon will be listed here.

Abstract

Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies.

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References

Gloyn A, Pearson E, Antcliff J, Proks P, Bruining G, Slingerland A . Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med. 2004; 350(18):1838-49. DOI: 10.1056/NEJMoa032922. View

Schols L, Kruger R, Amoiridis G, Przuntek H, Epplen J, Riess O . Spinocerebellar ataxia type 6: genotype and phenotype in German kindreds. J Neurol Neurosurg Psychiatry. 1998; 64(1):67-73. PMC: 2169927. DOI: 10.1136/jnnp.64.1.67. View

Lehmann-Horn F, Kuther G, Ricker K, Grafe P, Ballanyi K, Rudel R . Adynamia episodica hereditaria with myotonia: a non-inactivating sodium current and the effect of extracellular pH. Muscle Nerve. 1987; 10(4):363-74. DOI: 10.1002/mus.880100414. View

Cregg R, Cox J, Bennett D, Wood J, Werdehausen R . Mexiletine as a treatment for primary erythromelalgia: normalization of biophysical properties of mutant L858F NaV 1.7 sodium channels. Br J Pharmacol. 2014; 171(19):4455-63. PMC: 4209151. DOI: 10.1111/bph.12788. View

Fujiwara T, Sugawara T, Mazaki-Miyazaki E, Takahashi Y, Fukushima K, Watanabe M . Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures. Brain. 2003; 126(Pt 3):531-46. DOI: 10.1093/brain/awg053. View

Hirose S, Zenri F, Akiyoshi H, Fukuma G, Iwata H, Inoue T . A novel mutation of KCNQ3 (c.925T-->C) in a Japanese family with benign familial neonatal convulsions. Ann Neurol. 2000; 47(6):822-6. View

Links T, Zwarts M, Wilmink J, Molenaar W, OOSTERHUIS H . Permanent muscle weakness in familial hypokalaemic periodic paralysis. Clinical, radiological and pathological aspects. Brain. 1990; 113 ( Pt 6):1873-89. DOI: 10.1093/brain/113.6.1873. View

George Jr A, Crackower M, Abdalla J, Hudson A, Ebers G . Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita). Nat Genet. 1993; 3(4):305-10. DOI: 10.1038/ng0493-305. View

Miller T, Dias da Silva M, Miller H, Kwiecinski H, Mendell J, Tawil R . Correlating phenotype and genotype in the periodic paralyses. Neurology. 2004; 63(9):1647-55. DOI: 10.1212/01.wnl.0000143383.91137.00. View

10.

Jen J, Graves T, Hess E, Hanna M, Griggs R, Baloh R . Primary episodic ataxias: diagnosis, pathogenesis and treatment. Brain. 2007; 130(Pt 10):2484-93. DOI: 10.1093/brain/awm126. View

11.

Cummins T, Dib-Hajj S, Waxman S . Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. J Neurosci. 2004; 24(38):8232-6. PMC: 6729696. DOI: 10.1523/JNEUROSCI.2695-04.2004. View

12.

Sugawara T, Tsurubuchi Y, Agarwala K, Ito M, Fukuma G, Nagafuji H . A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction. Proc Natl Acad Sci U S A. 2001; 98(11):6384-9. PMC: 33477. DOI: 10.1073/pnas.111065098. View

13.

Pelzer N, Stam A, Haan J, Ferrari M, Terwindt G . Familial and sporadic hemiplegic migraine: diagnosis and treatment. Curr Treat Options Neurol. 2012; 15(1):13-27. DOI: 10.1007/s11940-012-0208-3. View

14.

Waters M, Minassian N, Stevanin G, Figueroa K, Bannister J, Nolte D . Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet. 2006; 38(4):447-51. DOI: 10.1038/ng1758. View

15.

Allen A, Cossette P, Delanty N, Eichler E, Goldstein D, Han Y . De novo mutations in epileptic encephalopathies. Nature. 2013; 501(7466):217-21. PMC: 3773011. DOI: 10.1038/nature12439. View

16.

Jen J, Kim G, Baloh R . Clinical spectrum of episodic ataxia type 2. Neurology. 2004; 62(1):17-22. DOI: 10.1212/01.wnl.0000101675.61074.50. View

17.

Novak K, Norman J, Mitchell J, Pinter M, Rich M . Sodium channel slow inactivation as a therapeutic target for myotonia congenita. Ann Neurol. 2014; 77(2):320-32. PMC: 4315705. DOI: 10.1002/ana.24331. View

18.

WALLACE R, Wang D, Singh R, Scheffer I, George Jr A, Phillips H . Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998; 19(4):366-70. DOI: 10.1038/1252. View

19.

Chen T, Klassen T, Goldman A, Marini C, Guerrini R, Noebels J . Novel brain expression of ClC-1 chloride channels and enrichment of CLCN1 variants in epilepsy. Neurology. 2013; 80(12):1078-85. PMC: 3662306. DOI: 10.1212/WNL.0b013e31828868e7. View

20.

DAdamo M, Gallenmuller C, Servettini I, Hartl E, Tucker S, Arning L . Novel phenotype associated with a mutation in the KCNA1(Kv1.1) gene. Front Physiol. 2015; 5:525. PMC: 4295438. DOI: 10.3389/fphys.2014.00525. View