Congenital myaesthenic syndrome

Gene: CHRNB1

Green List (high evidence)

CHRNB1 (cholinergic receptor nicotinic beta 1 subunit)
EnsemblGeneIds (GRCh38): ENSG00000170175
EnsemblGeneIds (GRCh37): ENSG00000170175
OMIM: 100710, Gene2Phenotype
CHRNB1 is in 4 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
?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314; Myasthenic syndrome, congenital, 2A, slow-channel, 616313; Slow channel myasthenic syndrome; fast channel myasthenic syndrome; Acetylcholine receptor deficiency syndrome; Myasthenic syndrome, slow-channel congenital, 601462; Congenital Myasthenic Syndrome, Dominant/Recessive

Rebecca Foulger (Genomics England curator)

Added the 'Deletions' tag based on the CHRNB1 mutation reported in Quiram et al., 1999 (PMID:10562302) which causes skipping of exon 8; this mutation was found in a compound heterozygous state in a patient with CMS2C (OMIM:616314).
Created: 26 Jan 2017, 3:30 p.m.
Comment when marking as ready: Green review plus 3 separate CHRNB1 cases listed in OMIM for Myasthenic syndromes.
Created: 26 Jan 2017, 3:30 p.m.
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, 3:07 p.m.
Comment on mode of inheritance: OMIM records biallelic inheritance for Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency (OMIM:616314) and monoallelic inheritance for Myasthenic syndrome, congenital, 2A, slow-channel (OMIM:616313).
Created: 26 Jan 2017, 3:06 p.m.
Comment on phenotypes: UKGTN test include CHRNB1 on their panel for Myasthenic syndrome, slow-channel congenital, 601462.
Created: 26 Jan 2017, 3 p.m.

David Beeson (Oxford University)

Green List (high evidence)

Mutations in CHRNB1 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; and acetylcholine receptor deficiency syndromes which are autosomal recessive.

Covered by the Oxford Congenital Myasthenia Service
Created: 24 Jan 2017, 4:46 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
  • ?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314
  • Myasthenic syndrome, congenital, 2A, slow-channel, 616313
  • Slow channel myasthenic syndrome
  • fast channel myasthenic syndrome
  • Acetylcholine receptor deficiency syndrome
  • Myasthenic syndrome, slow-channel congenital, 601462
  • Congenital Myasthenic Syndrome, Dominant/Recessive
Tags
deletions
OMIM
100710
Clinvar variants
Variants in CHRNB1
Penetrance
Complete
Publications
  • 8651643
  • 8872460
  • 22104196
  • 8651643
  • In 3 siblings with congenital myasthenic syndrome-2C associated with AChR deficiency (OMIM:616314), Quiram et al. (1999, PMID:10562302) identified compound heterozygosity for 2 mutations in the CHRNB1 gene.
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 CHRNB1.

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 CHRNB1. 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 publications

Rebecca Foulger (Genomics England curator)

Publications for CHRNB1 were set to 8651643; 8872460; 22104196; 8651643; In 3 siblings with congenital myasthenic syndrome-2C associated with AChR deficiency (OMIM:616314), Quiram et al. (1999, PMID:10562302) identified compound heterozygosity for 2 mutations in the CHRNB1 gene.

26 Jan 2017, Gel status: 4

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for CHRNB1 was changed to Other - please provide details in the comments

26 Jan 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for CHRNB1 were set to ?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314; Myasthenic syndrome, congenital, 2A, slow-channel, 616313; Slow channel myasthenic syndrome; fast channel myasthenic syndrome; Acetylcholine receptor deficiency syndrome; Myasthenic syndrome, slow-channel congenital, 601462; Congenital Myasthenic Syndrome, Dominant/Recessive

26 Jan 2017, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for CHRNB1 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 CHRNB1 were set to 22104196; 8651643; In 3 siblings with congenital myasthenic syndrome-2C associated with AChR deficiency (OMIM:616314), Quiram et al. (1999, PMID:10562302) identified compound heterozygosity for 2 mutations in the CHRNB1 gene.

26 Jan 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for CHRNB1 were set to ?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314 Myasthenic syndrome, congenital, 2A, slow-channel, 616313; Slow channel myasthenic syndrome; fast channel myasthenic syndrome; Acetylcholine receptor deficiency syndrome; Myasthenic syndrome, slow-channel congenital, 601462; Congenital Myasthenic Syndrome, Dominant/Recessive

28 Apr 2015, Gel status: 4

Added New Source

GEL ()

CHRNB1 was added to Congenital myaestheniapanel. Sources: Radboud University Medical Center, Nijmegen

28 Apr 2015, Gel status: 3

Added New Source

GEL ()

CHRNB1 was added to Congenital myaestheniapanel. Sources: UKGTN

28 Apr 2015, Gel status: 2

Added New Source

GEL ()

CHRNB1 was added to Congenital myaestheniapanel. Sources: Emory Genetics Laboratory

28 Apr 2015, Gel status: 1

Added New Source

GEL ()

CHRNB1 was added to Congenital myaestheniapanel. Sources: Illumina TruGenome Clinical Sequencing Services