Congenital myaesthenic syndrome
Gene: ALG14Comment on list classification: Promoted from red to green. ALG14 is associated with a phenotype on OMIM and not on Gene2Phenotype. This gene was promoted to green gene status based on the additional evidence provided by the expert reviewer as there is now enough evidence to support a gene-disease association.Created: 7 Aug 2019, 1:53 p.m. | Last Modified: 7 Aug 2019, 1:53 p.m.
Panel Version: 1.50
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.
In glycosylation pathway, just downstream of DPAGT1/GFPT1. forms complex with DPAGT1. knockdown of ALG14 shows reduction of AChR expression and shown to localise at endplate (Cossins). Schorling et al (28733338) describe 3 unrelated families (2 comp het, 1 hom) with ALG14 mutns. myasthenia demonstrated in 1 family (abnormal nerve conduction, responsive to CMS drugs). Therefore, at least 2 unrelated CMS families (Cossins and Schorling family A) with 2 more families with features that may fit (hypotonia, contractures - Schorling) plus some functional. upgrade to GreenCreated: 29 Apr 2019, 4:33 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Congenital myasthenic syndrome; ?Myasthenic syndrome, congenital, 15, without tubular aggregates, 616227
Publications
Comment on list classification: Updated rating from Grey to Red. 1 Green review (from gene submitter) but ALG14 Myasthenic mutations only reported in 1 family (PMID:23404334). Not confirmed on DD-G2P, and no other cases in current literature. No animal model.Created: 2 Feb 2017, 12:02 p.m.
In 2 European sisters with congenital myasthenic syndrome-15 (OMIM:616227), Cossins et al. (2013, PMID:23404334) identified compound heterozygous mutations in ALG14 (c.194C-T, P65L and c.310C-T,R104X).Created: 2 Feb 2017, 11:33 a.m.
Comment on mode of inheritance: Mode of inheritance confirmed by PMID:23404334 (compound heterozygotes identified).Created: 2 Feb 2017, 11:31 a.m.
Screening available through the Oxford Congenital Myasthenia ServiceCreated: 27 Jan 2017, 10:21 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Congenital myasthenic syndrome
Publications
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: ALG14 were changed from Congenital myasthenic syndrome; ?Myasthenic syndrome, congenital, 15, without tubular aggregates, 616227 to ?Myasthenic syndrome, congenital, 15, without tubular aggregates, OMIM:616227
Publications for gene: ALG14 were set to 28733338; 23404334
Gene: alg14 has been classified as Green List (High Evidence).
Publications for gene: ALG14 were set to 28733338; 23404334
Publications for gene: ALG14 were set to 28733338
Publications for gene ALG14 were changed from PMID: 23404334 to 28733338
Source NHS GMS was added to ALG14.
Source Wessex and West Midlands GLH was added to ALG14.
22 February 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.
This gene has been classified as Red List (Low Evidence).
Mode of inheritance for ALG14 was changed to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for ALG14 were set to Congenital myasthenic syndrome; ?Myasthenic syndrome, congenital, 15, without tubular aggregates, 616227
ALG14 was added to Congenital myaestheniapanel. Sources: Eligibility statement prior genetic testing
ALG14 was created by [email protected]