SCN1A Gene

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Karina Chen	+ 678 word(s)	678	2020-12-15 08:08:12

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/scn1a

sodium voltage-gated channel alpha subunit 1

genes

1. Normal Function

The SCN1A gene belongs to a family of genes that provide instructions for making sodium channels. These channels, which transport positively charged sodium atoms (sodium ions) into cells, play a key role in a cell's ability to generate and transmit electrical signals.

The SCN1A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.1. These channels are primarily found in the brain, where they control the flow of sodium ions into cells. NaV1.1 channels are involved in transmitting signals from one nerve cell (neuron) to another. Communication between neurons depends on chemicals called neurotransmitters, which are released from one neuron and taken up by neighboring neurons. The flow of sodium ions through NaV1.1 channels helps determine when neurotransmitters will be released.

2. Health Conditions Related to Genetic Changes

2.1. Familial hemiplegic migraine

At least seven mutations in the SCN1A gene have been identified in people with familial hemiplegic migraine type 3 (FHM3), a form of migraine headache that runs in families. Each of these mutations changes a single protein building block (amino acid) in the NaV1.1 channel, which alters the channel's structure. The abnormal channels stay open longer than usual, which increases the flow of sodium ions into neurons. This increase triggers the cell to release more neurotransmitters. The resulting changes in signaling between neurons make people with FHM3 more susceptible to developing these severe headaches.

2.2. Genetic epilepsy with febrile seizures plus

Hundreds of mutations in the SCN1A gene have been found to cause genetic epilepsy with febrile seizures plus (GEFS+), which is a spectrum of seizure disorders of varying severity. These conditions include simple febrile (fever-associated) seizures, which start in infancy and usually stop by age 5, and febrile seizures plus (FS+). FS+ involves febrile and other types of seizures, including those not related to fevers (afebrile seizures), that continue beyond childhood. The GEFS+ spectrum also includes other conditions, such as Dravet syndrome (also known as severe myoclonic epilepsy of infancy or SMEI), that cause more serious seizures that last longer and may be difficult to control. These recurrent seizures (epilepsy) can worsen over time and are often accompanied by a decline in brain function.

The SCN1A gene mutations that underlie GEFS+ have a variety of effects on the function of the NaV1.1 channel. Some mutations change single amino acids in the channel, which alter the channel's structure. Others lead to the production of a nonfunctional version of the NaV1.1 channel or reduce the number of these channels produced in each cell. Still other mutations change single amino acids in critical regions of the channel. All of these genetic changes affect the ability of NaV1.1 channels to transport sodium ions into neurons. Some mutations are thought to reduce channel activity while others may increase it. It is unclear, however, how these genetic changes underlie the development of seizures or why they lead to a range of seizure disorders with varying severity.

2.3. Other disorders

A common change (polymorphism) in the SCN1A gene has been associated with the effectiveness of certain anti-seizure medications. This polymorphism, which is written as ICS5N+5G>A, alters a single DNA building block (nucleotide) in the SCN1A gene. Studies suggest that this polymorphism is associated with the maximum safe amount (dose) of the anti-seizure drugs phenytoin and carbamazepine. These drugs treat epilepsy by blocking sodium channels (such as NaV1.1) in neurons. A dose that is too small may not control seizures effectively, while a dose that is too large may cause unwanted side effects. Researchers are hopeful that doctors will be able to test for the ICS5N+5G>A polymorphism to help determine the safest and most effective dose of anti-seizure medications for each individual.

3. Other Names for This Gene

GEFSP2
HBSCI
NAC1
Nav1.1
SCN1
SCN1A_HUMAN
sodium channel protein, brain I alpha subunit
sodium channel, voltage gated, type I alpha subunit
sodium channel, voltage-gated, type I, alpha
sodium channel, voltage-gated, type I, alpha polypeptide
sodium channel, voltage-gated, type I, alpha subunit

References

Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B, Biskup S, Ferrari MD, Herzog J, van den Maagdenberg AM, Pusch M, Strom TM. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine.Lancet. 2005 Jul 30-Aug 5;366(9483):371-7.
Fujiwara T. Clinical spectrum of mutations in SCN1A gene: severe myoclonicepilepsy in infancy and related epilepsies. Epilepsy Res. 2006 Aug;70 Suppl1:S223-30.
Gargus JJ, Tournay A. Novel mutation confirms seizure locus SCN1A is alsofamilial hemiplegic migraine locus FHM3. Pediatr Neurol. 2007 Dec;37(6):407-10.
Martin MS, Dutt K, Papale LA, Dubé CM, Dutton SB, de Haan G, Shankar A, Tufik S, Meisler MH, Baram TZ, Goldin AL, Escayg A. Altered function of the SCN1Avoltage-gated sodium channel leads to gamma-aminobutyric acid-ergic (GABAergic)interneuron abnormalities. J Biol Chem. 2010 Mar 26;285(13):9823-34. doi:10.1074/jbc.M109.078568.
Mulley JC, Scheffer IE, Petrou S, Dibbens LM, Berkovic SF, Harkin LA. SCN1Amutations and epilepsy. Hum Mutat. 2005 Jun;25(6):535-42. Review.
Pietrobon D. Familial hemiplegic migraine. Neurotherapeutics. 2007Apr;4(2):274-84. Review.
Spampanato J, Escayg A, Meisler MH, Goldin AL. Functional effects of twovoltage-gated sodium channel mutations that cause generalized epilepsy withfebrile seizures plus type 2. J Neurosci. 2001 Oct 1;21(19):7481-90.
Tate SK, Depondt C, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, Thom M,Sen A, Shorvon SD, Sander JW, Wood NW, Goldstein DB. Genetic predictors of themaximum doses patients receive during clinical use of the anti-epileptic drugscarbamazepine and phenytoin. Proc Natl Acad Sci U S A. 2005 Apr12;102(15):5507-12.
Tate SK, Singh R, Hung CC, Tai JJ, Depondt C, Cavalleri GL, Sisodiya SM,Goldstein DB, Liou HH. A common polymorphism in the SCN1A gene associates withphenytoin serum levels at maintenance dose. Pharmacogenet Genomics. 2006Oct;16(10):721-6.
Vanmolkot KR, Babini E, de Vries B, Stam AH, Freilinger T, Terwindt GM, NorrisL, Haan J, Frants RR, Ramadan NM, Ferrari MD, Pusch M, van den Maagdenberg AM,Dichgans M. The novel p.L1649Q mutation in the SCN1A epilepsy gene is associated with familial hemiplegic migraine: genetic and functional studies. Mutation inbrief #957. Online. Hum Mutat. 2007 May;28(5):522.
Volkers L, Kahlig KM, Verbeek NE, Das JH, van Kempen MJ, Stroink H, Augustijn P, van Nieuwenhuizen O, Lindhout D, George AL Jr, Koeleman BP, Rook MB. Nav 1.1dysfunction in genetic epilepsy with febrile seizures-plus or Dravet syndrome.Eur J Neurosci. 2011 Oct;34(8):1268-75. doi: 10.1111/j.1460-9568.2011.07826.x.
Yamakawa K. Na channel gene mutations in epilepsy--the functionalconsequences. Epilepsy Res. 2006 Aug;70 Suppl 1:S218-22.Review.

©Text is available under the terms and conditions of the Creative Commons-Attribution ShareAlike (CC BY-SA) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Genetics & Heredity

Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Karina Chen

View Times: 352

Entry Collection: MedlinePlus

Update Date: 24 Dec 2020

Table of Contents

Video Upload Options

Confirm