Congenital myaesthenic syndrome
Gene: CHRNA1Comment on phenotypes: Previous 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 syndromeCreated: 22 Mar 2021, 1:12 p.m. | Last Modified: 22 Mar 2021, 1:12 p.m.
Panel Version: 2.14
Comment on publications: 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.Created: 22 Mar 2021, 1:12 p.m. | Last Modified: 22 Mar 2021, 1:12 p.m.
Panel Version: 2.13
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
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
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.
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
Phenotypes for gene: CHRNA1 were changed from 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 to Myasthenic syndrome, congenital, 1A, slow-channel, OMIM:601462; Myasthenic syndrome, congenital, 1B, fast-channel, OMIM:608930
Publications for gene: 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.
Source NHS GMS was added to CHRNA1.
Source Wessex and West Midlands GLH was added to CHRNA1. 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).
Mode of pathogenicity for CHRNA1 was changed to Other - please provide details in the comments
Mode of inheritance for CHRNA1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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.
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
CHRNA1 was added to Congenital myaestheniapanel. Sources: Radboud University Medical Center, Nijmegen
CHRNA1 was added to Congenital myaestheniapanel. Sources: UKGTN
CHRNA1 was added to Congenital myaestheniapanel. Sources: Emory Genetics Laboratory
CHRNA1 was added to Congenital myaestheniapanel. Sources: Illumina TruGenome Clinical Sequencing Services