Congenital myaesthenic syndrome

Gene: ALG14

Comment 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

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)

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 Green

Created: 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

• 28733338

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.

Green List (high evidence)

Screening available through the Oxford Congenital Myasthenia Service

Created: 27 Jan 2017, 10:21 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital myasthenic syndrome

Publications

• PMID: 23404334

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