Congenital myaesthenic syndrome

Gene: CHRNA1

Green List (high evidence)

CHRNA1 (cholinergic receptor nicotinic alpha 1 subunit)
EnsemblGeneIds (GRCh38): ENSG00000138435
EnsemblGeneIds (GRCh37): ENSG00000138435
OMIM: 100690, Gene2Phenotype
CHRNA1 is in 6 panels

4 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
Created: 29 Apr 2019, 4:33 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Congenital Myasthenic Syndrome, Dominant/Recessive; Myasthenic syndrome, congenital, 1A, slow-channel, 601462; Myasthenic syndrome, congenital, 1B, fast-channel, 608930; Slow channel myasthenic syndrome; fast channel myasthenic syndrome; Acetylcholine receptor deficiency syndrome

Rebecca Foulger (Genomics England curator)

Comment on mode of pathogenicity: The 'Slow-channel' form of myasthenic syndrome results from kinetic abnormalities of the AChR channel, specifically prolonged opening and activity of the channel (gain of function).
Created: 26 Jan 2017, 2:49 p.m.
Comment when marking as ready: Green review plus >3 cases of CHRNA1 mutations causing Congenital Myasthenic Syndromes (OMIM:601462 and 608930).
Created: 26 Jan 2017, 2:41 p.m.
Comment on mode of inheritance: OMIM support both monoallelic and biallelic inheritance: CHRNA1 shows autosomal dominant inheritance for Myasthenic syndrome, congenital, 1A, slow-channel, 601462. For Myasthenic syndrome, congenital, 1B, fast-channel, 608930 inheritance is generally biallelic, with one reported case of autosomal dominant (PMID:15079006).
Created: 26 Jan 2017, 2:30 p.m.

David Beeson (Oxford University)

Green List (high evidence)

Mutations in CHRNA can give rise to the slow channel myasthenic syndrome that autosomal dominant and results in a gain of function; fast channel congenital myasthenic syndromes that are autosomal recessive (with one published exception); and acetylcholine receptor deficiency syndromes which are autosomal recessive.
Created: 24 Jan 2017, 4:35 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Slow channel myasthenic syndrome; fast channel myasthenic syndrome; Acetylcholine receptor deficiency syndrome

Publications

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Wessex and West Midlands GLH
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Congenital Myasthenic Syndrome, Dominant/Recessive
  • Myasthenic syndrome, congenital, 1A, slow-channel, 601462
  • Myasthenic syndrome, congenital, 1B, fast-channel, 608930
  • Slow channel myasthenic syndrome
  • fast channel myasthenic syndrome
  • Acetylcholine receptor deficiency syndrome
OMIM
100690
Clinvar variants
Variants in CHRNA1
Penetrance
Complete
Publications
  • 7619526
  • 15034283
  • PMID:15079006 (Webster et al., 2004) report the heterozygous CHRNA1 mutation causing fast-channel congenital myasthenic syndrome-1B (OMIM:608930). The other reports for this disorder are for biallelic mutations.
Mode of Pathogenicity
Other - please provide details in the comments
Panels with this gene

History Filter Activity

29 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to CHRNA1.

29 Apr 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to CHRNA1. Rating Changed from Green List (high evidence) to Green List (high evidence)

22 Feb 2017, Gel status: 4

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.

26 Jan 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

26 Jan 2017, Gel status: 4

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for CHRNA1 was changed to Other - please provide details in the comments

26 Jan 2017, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for CHRNA1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

26 Jan 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for CHRNA1 were set to 7619526; 15034283; PMID:15079006 (Webster et al., 2004) report the heterozygous CHRNA1 mutation causing fast-channel congenital myasthenic syndrome-1B (OMIM:608930). The other reports for this disorder are for biallelic mutations.

26 Jan 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for CHRNA1 were set to Congenital Myasthenic Syndrome, Dominant/Recessive; Myasthenic syndrome, congenital, 1A, slow-channel, 601462; Myasthenic syndrome, congenital, 1B, fast-channel, 608930; Slow channel myasthenic syndrome; fast channel myasthenic syndrome; Acetylcholine receptor deficiency syndrome

28 Apr 2015, Gel status: 4

Added New Source

GEL ()

CHRNA1 was added to Congenital myaestheniapanel. Sources: Radboud University Medical Center, Nijmegen

28 Apr 2015, Gel status: 3

Added New Source

GEL ()

CHRNA1 was added to Congenital myaestheniapanel. Sources: UKGTN

28 Apr 2015, Gel status: 2

Added New Source

GEL ()

CHRNA1 was added to Congenital myaestheniapanel. Sources: Emory Genetics Laboratory

28 Apr 2015, Gel status: 1

Added New Source

GEL ()

CHRNA1 was added to Congenital myaestheniapanel. Sources: Illumina TruGenome Clinical Sequencing Services