Adult onset neurodegenerative disorder

Gene: POLG

Green List (high evidence)

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

Created: 11 Mar 2026, 10:56 a.m. | Last Modified: 11 Mar 2026, 10:56 a.m.

Panel Version: 8.15

Green List (high evidence)

Comment on publications: PMID: 39498811 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 12 Mar 2025, 2:51 p.m. | Last Modified: 12 Mar 2025, 2:51 p.m.

Panel Version: 7.10

In their study of a 1185 Spanish Parkinson disease patients, PMID: 39498811 report eleven individuals carrying heterozygous POLG variants. Seven POLG variants were identified in the patients, including the co-occurrence of c.752C>T, p.Thr251Ile and c.1760C>Tp.Pro587Leu (NM_002693.3), which are in cis. The phenotypic features of these patients included motor fluctuations (81.8%), dyskinesias (70%), cognitive impairment (80%), rapid eye movement sleep behavior disorder (70%) and olfactory dysfunction (71.4%). Ataxia or peripheral neuropathy were not reported for these patients (PMID: 39498811).

Created: 12 Mar 2025, 2:49 p.m. | Last Modified: 12 Mar 2025, 2:50 p.m.

Panel Version: 7.8

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• 39498811

Green List (high evidence)

SANDO is an autosomal recessive systemic disorder characterized mainly by adult onset of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis . Spinocerebellar ataxia with epilepsy (SCAE) is a similar disorder with a higher frequency of migraine headaches and seizures. Progressive. >3 cases

Created: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.

Panel Version: 1.99

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE)

Red List (low evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE)

Red List (low evidence)

As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red

Created: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.

Panel Version: 1.106

Review and rating from 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. All the green and amber, except for the genes with triplet repeats, were reviewed.

Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.

Panel Version: 1.101

Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.

Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.

Panel Version: 1.74

Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.

Created: 23 Apr 2019, 5:35 p.m.

Red List (low evidence)