Human Disease Model Report: progressive external ophthalmoplegia with mtDNA deletions, autosomal dominant 1

General Information

Name

progressive external ophthalmoplegia with mtDNA deletions, autosomal dominant 1

FlyBase ID

FBhh0000445

Disease Ontology Term

autosomal dominant progressive external ophthalmoplegia 1

Parent Disease

progressive external ophthalmoplegia with mtDNA deletions

OMIM

PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 1; PEOA1

Overview

This report describes progressive external ophthalmoplegia with mtDNA deletions, autosomal dominant 1 (PEOA1); this is one of several diseases associated with the human DNA polymerase gene POLG, which plays a role in replication of mitochondrial DNA. OMIM includes this disease in the phenotypic series progressive external ophthalmoplegia with mtDNA deletions. There is a single fly ortholog of POLG, Dmel\PolG1, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. See also the human disease model report for mtDNA polymerase disorders, POLG-related (FBhh0000432) for additional information on experimental results using Drosophila models of this and related diseases.

The human POLG gene has not been introduced into flies.

Experiments characterizing mutations in the fly gene analogous to variants implicated in POLG-related disorders include two implicated in PEOA1. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): Y873C in the fly PolG1 gene (corresponds to Y955C in the human POLG gene); Y873H in the fly PolG1 gene (corresponds to Y955H in the human POLG gene).

[updated Apr. 2018 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: progressive external ophthalmoplegia with mtDNA deletions

Symptoms and phenotype

Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. Both autosomal dominant and autosomal recessive inheritance can occur; autosomal recessive inheritance is usually more severe (Filosto et al., 2003, pubmed:12975295; Luoma et al., 2004, pubmed:15351195) [from MIM:157640; 2019.02.19]

(OMIM, 2013-)

Specific Disease Summary: progressive external ophthalmoplegia with mtDNA deletions, autosomal dominant 1

OMIM report

[PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 1; PEOA1](https://omim.org/entry/157640)

Human gene(s) implicated

[POLYMERASE, DNA, GAMMA; POLG](https://omim.org/entry/174763)

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

External links

Gene2Function (human gene): POLG
Gene Cards: POLG
MedlinePlus (condition): progressive external ophthalmoplegia
MedlinePlus (gene): POLG
MARRVEL (human gene): POLG
NCBI MedGen: Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1)
NCBI (Entrez) gene: POLG; DNA polymerase gamma, catalytic subunit

Disease synonyms

PEOA1

progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1

Related Diseases

Related human health report(s)

mtDNA polymerase disorders, POLG-related

Related Specific Diseases

OMIM phenotypic series

Progressive external ophthalmoplegia with mtDNA deletions

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[PEOA1](https://omim.org/entry/157640)

[POLG](https://omim.org/entry/174763)

progressive external ophthalmoplegia with mtDNA deletions, autosomal dominant 1

[PEOA2](https://omim.org/entry/609283)

[SLC25A4](https://omim.org/entry/103220)

progressive external ophthalmoplegia with mtDNA deletions, autosomal dominant 2

[PEOA3](https://omim.org/entry/609286)

[TWNK](https://omim.org/entry/606075)

progressive external ophthalmoplegia with mtDNA deletions, autosomal dominant 3

[PEOA4](https://omim.org/entry/610131)

[POLG2](https://omim.org/entry/604983)

progressive external ophthalmoplegia with mtDNA deletions, autosomal dominant 4

[PEOB1](https://omim.org/entry/258450)

[POLG](https://omim.org/entry/174763)

progressive external ophthalmoplegia with mtDNA deletions, autosomal recessive 1

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

POLG; DNA polymerase gamma, catalytic subunit

D. melanogaster ortholog (based on DIOPT)

Dmel\PolG1

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\PolG1

Gene Snapshot

DNA polymerase gamma subunit 1 (PolG1) encodes the catalytic subunit of mitocondrial DNA polymerase gamma, which is responsible for the replication and repair of the mitochondrial genome. [Date last reviewed: 2019-12-19]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Ortholog of human POLG (1 Drosophila to 1 human). Dmel\PolG1 shares 44% identity and 58% similarity with human POLG.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (1 groups)

PolG1

protein-protein