Childhood onset hereditary spastic paraplegia

Gene: MAG

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosoma lfollowing NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 5:14 p.m. | Last Modified: 10 Oct 2023, 5:17 p.m.

Panel Version: 4.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

At least 12 individuals from 8 families have been identified with biallelic variants in this gene. Clinical features are characterised by spasticity (9/13), neuropathy (8/13), optic atrophy (7/13), variable cognitive deficits (7/13), and cerebellar signs (10/13) including ataxia in some (8/13) although 3/10 showed normal brain MRI results.

Created: 27 Feb 2023, 4:01 p.m. | Last Modified: 27 Feb 2023, 4:01 p.m.

Panel Version: 3.17

Green List (high evidence)

Eight unrelated families reported.

Created: 19 Sep 2020, 7:47 a.m. | Last Modified: 19 Sep 2020, 7:47 a.m.

Panel Version: 2.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 75, autosomal recessive, MIM# 616680

Publications

• 24482476
• 26179919
• 31402626
• 32629324

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

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

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.

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