Curation CPEO POLG

Gene POLG

Disease CPEO

Inheritance –

Score

6 + 1 = 7 / 18

Genetic + experimental = total

Classification

Disputed

Refuted

Moderate

Definitive

Last Updated 08/18/2025

Pubs Reviewed 1

Publication Span –

Publication Interval –

Curator(s) Macayla Weiner, Laurel Hiatt

Description

The curated POLG CAG/polyglutamine repeat has disputed relevance to CPEO. The provided sources evaluate the repeat primarily as a modifier/association signal in Parkinson disease and Friedreich ataxia, and note that pathogenic POLG coding variants can cause progressive external ophthalmoplegia; they do not provide direct evidence that POLG CAG-repeat variation causes CPEO.

All criTRia Curations Locus Page

Genetic evidence

Total: 6

Per page

Category	Type	Citation	Score	Details
Singular Evidence	Probands	PMID:22963882	6	Reports 191 Parkinson disease cases and 191 controls sequenced for the POLG1 CAG repeat; it does not describe CPEO probands.

Experimental evidence

Total: 1

Per page

Category	Type	Citation	Score	Details
Function	Biochemical function	PMID:22963882	0.5	Gene-level evidence: POLG encodes the catalytic subunit of mitochondrial DNA polymerase gamma, which replicates and repairs mtDNA; PMID 22963882 does not provide a CPEO-specific functional assay of the CAG repeat.
Function	Protein interaction	PMID:22963882	0.5	Gene-level evidence: polymerase gamma is described as a heterotrimer comprising one POLG1 catalytic subunit and two POLG2 accessory subunits; no CAG-repeat- or CPEO-specific altered interaction is shown.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.