Congenital myaesthenic syndrome

Gene: CHRNA1

Comment 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 syndrome

Created: 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

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
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.

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

• PMID: 7619526
• PMID: 15034283
• PMID: 15079006

Mode of pathogenicity
Other

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