Congenital myaesthenic syndrome

Gene: ALG2

Green List (high evidence)

ALG2 (ALG2, alpha-1,3/1,6-mannosyltransferase)
EnsemblGeneIds (GRCh38): ENSG00000119523
EnsemblGeneIds (GRCh37): ENSG00000119523
OMIM: 607905, Gene2Phenotype
ALG2 is in 11 panels

4 reviews

Louise Daugherty (Genomics England Curator)

I don't know

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.

Michael Oldridge (NHS)

Green List (high evidence)

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

Rebecca Foulger (Genomics England curator)

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.

David Beeson (Oxford University)

Green List (high evidence)

Screening available through the Oxford Congenital Myasthenia Service
Created: 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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
  • Wessex and West Midlands GLH
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
Phenotypes
  • Congenital myasthenic syndromes
  • Myasthenic syndrome, congenital, 14, with tubular aggregates, 616228
  • Congenital disorder of glycosylation CDG type Ii, 607906
OMIM
607905
Clinvar variants
Variants in ALG2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

16 Oct 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: alg2 has been classified as Green List (High Evidence).

29 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to ALG2.

29 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to ALG2.

22 Feb 2017, Gel status: 2

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

22 February 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.

22 Feb 2017, Gel status: 2

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Amber List (Moderate Evidence).

31 Jan 2017, Gel status: 2

Upload gene information

Rebecca Foulger (Genomics England curator)

ALG2 was added to Congenital myaestheniapanel. Sources: Radboud University Medical Center, Nijmegen

31 Jan 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

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

31 Jan 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for ALG2 was changed to BIALLELIC, autosomal or pseudoautosomal

31 Jan 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for ALG2 were set to 23404334

31 Jan 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for ALG2 were set to Congenital myasthenic syndromes; Myasthenic syndrome, congenital, 14, with tubular aggregates; Congenital disorder of glycosylation CDG type Ii, 607906

28 Apr 2015, Gel status: 1

Added New Source

GEL ()

ALG2 was added to Congenital myaestheniapanel. Sources: Emory Genetics Laboratory