Hereditary neuropathy or pain disorder

Gene: GAN

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 1:11 p.m. | Last Modified: 26 Sep 2024, 1:11 p.m.

Panel Version: 5.16

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on list classification: This gene should be promoted to Green at the next GMS panel update as the scope of this panel has now been expanded to include complex cases of neuropathy.
Biallelic variants in the GAN gene cause giant axonal neuropathy. This childhood onset polyneuropathy results in progressive neurodegeneration of both the peripheral and central nervous systems. More than 10 unrelated cases have been reported in the literature which is sufficient for making this gene Green (PMIDs: 18595793; 19231187; 20949505; 27852232; 36866531)

Created: 17 Apr 2024, 3:26 p.m. | Last Modified: 17 Apr 2024, 3:26 p.m.

Panel Version: 3.91

Green List (high evidence)

GAN-related neurodegeneration comprises a phenotypic continuum ranging from severe (sometimes called classic giant axonal neuropathy) to milder pure early-onset peripheral motor and sensory neuropathies. The classic giant axonal neuropathy phenotype typically manifests as an infantile-onset neurodegenerative disorder, starting as a severe peripheral motor and sensory neuropathy and evolving into central nervous system impairment (intellectual disability, seizures, cerebellar signs, and pyramidal tract signs).

Created: 31 Jan 2024, 9:14 a.m. | Last Modified: 31 Jan 2024, 9:14 a.m.

Panel Version: 3.82

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neuropathy; intellectual disability

Publications

• 20301315

Green List (high evidence)

In Bristol 4x C4 (one said to have giant axonal neuropathy). First paper PMID:11062483 identifying GAN gene in giant axonal neuropathy. Multiple papers since on HGMD

Created: 29 Apr 2019, 12:30 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Giant axonal neuropathy-1

Publications

• 1106248

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

I don't know

This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.

Created: 6 Dec 2019, 8:24 p.m. | Last Modified: 6 Dec 2019, 8:24 p.m.

Panel Version: 0.63

Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)

Created: 6 Dec 2019, 8:20 p.m. | Last Modified: 6 Dec 2019, 8:20 p.m.

Panel Version: 0.59

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, 5 p.m.

Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 29 Apr 2019, 12:53 p.m.

Green List (high evidence)

Green List (high evidence)

Green List (high evidence)

should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46

Created: 17 Mar 2024, 9:05 p.m. | Last Modified: 17 Mar 2024, 9:05 p.m.

Panel Version: 3.83

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on list classification: Promoted from amber to green due to agreement from 3 reviewers.

Created: 4 May 2016, 8:46 a.m.