Hereditary spastic paraplegia - childhood onset

Gene: MAG

Amber List (moderate evidence)

MAG (myelin associated glycoprotein)
EnsemblGeneIds (GRCh38): ENSG00000105695
EnsemblGeneIds (GRCh37): ENSG00000105695
OMIM: 159460, Gene2Phenotype
MAG is in 4 panels

3 reviews

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

I don't know

Two families reported currently. Childhood onset. No additional patients identified using Sheffield panel.
Created: 10 May 2019, 7:23 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Louise Daugherty (Genomics England Curator)

I don't know

Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Created: 21 May 2019, 4:50 p.m.
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 4:54 p.m.
Amber rating on Hereditary spastic paraplegia panel 1.198

Comment on list classification: Updated rating from Grey to Amber: Gene added and rated red by Chris Buxton (Bristol NHS) based on 1 family in PMID:24482476. One additional family reported in PMID:26179919 but require at least one further case for diagnostic rating.
Rebecca Foulger (Genomics England curator), 18 Dec 2018

In 3 siblings with AR spastic paraplegia born of consanguineous Palestinian parents, Lossos et al. (2015, PMID:26179919) identified a homozygous c.399C-G transversion in the MAG gene (S133R).
Rebecca Foulger (Genomics England curator), 18 Dec 2018

PMID:24482476 (Novarino et al 2014) identified MAG as a HSP candidate gene based on the HSPome (network analysis). In 2 affected sisters from a consanguineous family (family 1226) with AR spastic paraplegia-75, PMID:24482476 identified homozygosity for a c.1288T-G transversion in the MAG gene (C430G).
Rebecca Foulger (Genomics England curator), 18 Dec 2018

1 family Novarino (2014, 24482476). Homozygous Cys430Gly with HSp phenotype. No other detail. 1 family. Limited evidence Diagnostic on Sheffield HSP panel Sources: Literature
Chris Buxton (North Bristol NHS Trust), 27 Nov 2018. Submitted Red rating.
Created: 2 May 2019, 4:19 p.m.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

Victoria: spastic paraplegia and cognitive impairment in childhood. 2 cases published in literature with spastic paraplegia. In sheffields HSP panel
Created: 28 Apr 2019, 4:16 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 75, autosomal recessive, 616680

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Yorkshire and North East GLH
  • Expert Review Amber
  • NHS GMS
  • London North GLH
  • Literature
Phenotypes
  • Spastic paraplegia 75, autosomal recessive, 616680
OMIM
159460
Clinvar variants
Variants in MAG
Penetrance
None
Publications
Panels with this gene

History Filter Activity

13 May 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to MAG.

2 May 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: mag has been classified as Amber List (Moderate Evidence).

28 Apr 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

28 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to MAG.

28 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to MAG.

3 Apr 2019, Gel status: 2

Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Added phenotypes Spastic paraplegia 75, autosomal recessive, 616680 for gene: MAG Publications for gene MAG were changed from 24482476; 26179919 to 26179919; 24482476

28 Jan 2019, Gel status: 2

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Rebecca Foulger: Comment on list classification

19 Dec 2018, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Sarah Leigh (Genomics England Curator)

gene: MAG was added gene: MAG was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Amber,Literature Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAG were set to 24482476; 26179919 Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, 616680