Congenital myaesthenic syndrome

Gene: SCN4A

Green List (high evidence)

SCN4A (sodium voltage-gated channel alpha subunit 4)
EnsemblGeneIds (GRCh38): ENSG00000007314
EnsemblGeneIds (GRCh37): ENSG00000007314
OMIM: 603967, Gene2Phenotype
SCN4A is in 14 panels

3 reviews

Louise Daugherty (Genomics England Curator)

I don't know

Review and rating from Michael Oldridge (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust), submitted by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.
Created: 30 Apr 2019, 9:30 a.m.

Michael Oldridge (NHS)

Green List (high evidence)

see PanelApp - extra case described (see publication)
Created: 29 Apr 2019, 4:33 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 16, 614198; Congenital Myasthenic Syndrome, Recessive; congenital myasthenic syndromes

Publications

  • http://dx.doi.org/10.1016/j.nmd.2015.06.091

Rebecca Foulger (Genomics England curator)

Mutations in SCN4A, encoding the Na V 1.4 sodium channel of skeletal muscle, have been identified in patients with a group of related muscular disorders including myotonia, periodic paralysis, myasthenia, and congenital myopathy. Most mutations are missense with gain-of-function defects. Loss-of-function from enhanced inactivation or null alleles is rare and underlies congenital myasthenia [Source: PMID:27048647].
Created: 31 Jan 2017, 2:34 p.m.
PMID:27048647 (Wu et al,. 2016) present a mouse model: using an NaV1.4 (SCN4A) knock-out mouse, Wu et al . show that haploinsufficiency gives rise to latent myasthenia, but not periodic paralysis.
Created: 31 Jan 2017, 2:33 p.m.
Habbout et al., 2016 (PMID:26659129) present a proband with fatigable muscle weakness characteristic of congenital myasthenic syndrome with acute and reversible attacks, and a novel (loss-of-function) homozygous SCN4A mutation (p.R1454W).
Created: 31 Jan 2017, 2:25 p.m.
In a 57-year-old woman, born of consanguineous parents, with CMS16 (OMIM:614198), Arnold et al. (2015, PMID:25707578) identified a homozygous missense mutation in the SCN4A gene (R1457H).
Created: 31 Jan 2017, 2:11 p.m.
In a patient with congenital myasthenic syndrome-16 (OMIM:614198) associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth, Tsujino et al. (2003, PMID:12766226) identified compound heterozygous variants in the SCN4A gene (V1442E and S246L).
Created: 31 Jan 2017, 2:11 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Wessex and West Midlands GLH
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Myasthenic syndrome, congenital, 16, 614198
  • Congenital Myasthenic Syndrome, Recessive
  • congenital myasthenic syndromes
OMIM
603967
Clinvar variants
Variants in SCN4A
Penetrance
Complete
Publications
  • http://dx.doi.org/10.1016/j.nmd.2015.06.091
Panels with this gene

History Filter Activity

29 Apr 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene SCN4A were changed from to http://dx.doi.org/10.1016/j.nmd.2015.06.091

29 Apr 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to SCN4A.

29 Apr 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to SCN4A.

22 Feb 2017, Gel status: 3

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

22 February 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.

31 Jan 2017, Gel status: 3

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for SCN4A were set to Myasthenic syndrome, congenital, 16, 614198; Congenital Myasthenic Syndrome, Recessive; congenital myasthenic syndromes;

31 Jan 2017, Gel status: 3

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for SCN4A were set to Myasthenic syndrome, congenital, 16, 614198; Congenital Myasthenic Syndrome, Recessive;

31 Jan 2017, Gel status: 3

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for SCN4A were set to Myasthenic syndrome, congenital, 16, 614198; Congenital Myasthenic Syndrome, Recessive; Hyperkalemic periodic paralysis, type 2, 170500

28 Apr 2015, Gel status: 3

Added New Source

GEL ()

SCN4A was added to Congenital myaestheniapanel. Sources: Radboud University Medical Center, Nijmegen

28 Apr 2015, Gel status: 2

Added New Source

GEL ()

SCN4A was added to Congenital myaestheniapanel. Sources: Emory Genetics Laboratory

28 Apr 2015, Gel status: 1

Added New Source

GEL ()

SCN4A was added to Congenital myaestheniapanel. Sources: Illumina TruGenome Clinical Sequencing Services