Congenital myaesthenic syndrome

Gene: CHRNB1

Comment 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/Recessive

Created: 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

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.

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

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.

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

• PMID 8651643
• PMID: 22104196

Mode of pathogenicity
Other

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