Congenital myaesthenic syndrome
Gene: ALG2Comment on phenotypes: Previous phenotypes:
Congenital myasthenic syndromes;Myasthenic syndrome, congenital, 14, with tubular aggregates, 616228;Congenital disorder of glycosylation CDG type Ii, 607906Created: 22 Mar 2021, 1:09 p.m. | Last Modified: 22 Mar 2021, 1:09 p.m.
Panel Version: 2.11
Comment on list classification: Upgraded from Amber to Green. Appropriate phenotypes, sufficient cases (with functional work), and external review comment all support gene-disease association.Created: 16 Oct 2019, 11:12 a.m. | Last Modified: 16 Oct 2019, 11:12 a.m.
Panel Version: 1.54
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.
Seen in 2 unrelated families, segregation data (Cossins et al) in these families fits with AR (7 from 1 family, 5 from the other, in addition to probands), significant LOD?. functional work shows downregulation of expression in vitro and vivo. In glycosylation pathway, just downstream of DPAGT1. phenotype mirrors that of DPAGT1 patients.Created: 29 Apr 2019, 4:33 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Congenital myasthenic syndromes; Myasthenic syndrome, congenital, 14, with tubular aggregates, 616228; Congenital disorder of glycosylation CDG type Ii, 607906
Comment on list classification: Kept rating as Amber awaiting further evidence: 3 cases but the individuals from Cossins (2013) and Monies (2014) are most likely from the same Bedouin kindred. Therefore only 2 unrelated cases reported so far.Created: 22 Feb 2017, 12:11 p.m.
In an man, born of consanguineous Italian parents, with congenital myasthenic syndrome-14 (CMS14; 616228), Cossins et al. (2013, PMID:23404334) identified a homozygous c.203T-G transversion in exon 1 of the ALG2 gene (V68G).Created: 31 Jan 2017, 4:01 p.m.
In 3 patients from a large consanguineous Saudi Arabian Bedouin family with CMS14, Monies et al. (2014, PMID:24461433) identified the same homozygous del/ins mutation in exon 1 of the ALG2 gene as that found by Cossins et al. (PMID:23404334). The families reported by Monies et al. (2014) and Cossins et al. (2013) both originated from the same small village, suggesting a common founder.Created: 31 Jan 2017, 4 p.m.
In 4 siblings, born of consanguineous Saudi Arabian parents, with congenital myasthenic syndrome-14 (OMIM:616228), Cossins et al. (2013, PMID:23404334) identified a homozygous ins/del mutation in the ALG2 gene: c.214_226del/ins, resulting in the replacement of several conserved residues (p.72_75delGDWLinsSPR).Created: 31 Jan 2017, 3:58 p.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM.Created: 31 Jan 2017, 3:57 p.m.
Screening available through the Oxford Congenital Myasthenia ServiceCreated: 27 Jan 2017, 9:24 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Congenital myasthenic syndrome; Congenital disorder of glycosylation CDG type Ii (MIM 607906).
Publications
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: ALG2 were changed from Congenital myasthenic syndromes; Myasthenic syndrome, congenital, 14, with tubular aggregates, 616228; Congenital disorder of glycosylation CDG type Ii, 607906 to Myasthenic syndrome, congenital, 14, with tubular aggregates, OMIM:616228
Gene: alg2 has been classified as Green List (High Evidence).
Source NHS GMS was added to ALG2.
Source Wessex and West Midlands GLH was added to ALG2.
22 February 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.
This gene has been classified as Amber List (Moderate Evidence).
ALG2 was added to Congenital myaestheniapanel. Sources: Radboud University Medical Center, Nijmegen
Phenotypes for ALG2 were set to Congenital myasthenic syndromes; Myasthenic syndrome, congenital, 14, with tubular aggregates, 616228; Congenital disorder of glycosylation CDG type Ii, 607906
Mode of inheritance for ALG2 was changed to BIALLELIC, autosomal or pseudoautosomal
Publications for ALG2 were set to 23404334
Phenotypes for ALG2 were set to Congenital myasthenic syndromes; Myasthenic syndrome, congenital, 14, with tubular aggregates; Congenital disorder of glycosylation CDG type Ii, 607906
ALG2 was added to Congenital myaestheniapanel. Sources: Emory Genetics Laboratory