Congenital myaesthenic syndrome
Gene: CHRNB1Comment on phenotypes: Previous 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/RecessiveCreated: 22 Mar 2021, 1:15 p.m. | Last Modified: 22 Mar 2021, 1:15 p.m.
Panel Version: 2.16
Comment on publications: 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.Created: 22 Mar 2021, 1:13 p.m. | Last Modified: 22 Mar 2021, 1:13 p.m.
Panel Version: 2.15
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.
see PanelAppCreated: 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
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.
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 ServiceCreated: 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
Phenotypes for gene: CHRNB1 were changed from ?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 to ?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, OMIM:616314; Myasthenic syndrome, congenital, 2A, slow-channel, OMIM:616313
Publications for gene: 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.
Source NHS GMS was added to CHRNB1.
Source Wessex and West Midlands GLH was added to CHRNB1. Rating Changed from Green List (high evidence) to Green List (high evidence)
22 February 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.
This gene has been classified as Green List (High Evidence).
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.
Mode of pathogenicity for CHRNB1 was changed to Other - please provide details in the comments
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
Mode of inheritance for CHRNB1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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.
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
CHRNB1 was added to Congenital myaestheniapanel. Sources: Radboud University Medical Center, Nijmegen
CHRNB1 was added to Congenital myaestheniapanel. Sources: UKGTN
CHRNB1 was added to Congenital myaestheniapanel. Sources: Emory Genetics Laboratory
CHRNB1 was added to Congenital myaestheniapanel. Sources: Illumina TruGenome Clinical Sequencing Services