Expert Reviewed By: Dr. Brandon Colby MD
Progressive external ophthalmoplegia (PEO) is a rare genetic disorder characterized by the gradual weakening of the eye muscles, leading to difficulty in moving the eyes and drooping eyelids. In some cases, PEO is associated with multiple mitochondrial DNA (mtDNA) deletions, which result in a more severe form of the disease. This article aims to provide an overview of the current understanding of digenic PEO with mtDNA deletions, the process of diagnosing this condition, and the role of genetic testing in managing the disease.
Understanding Digenic Progressive External Ophthalmoplegia with mtDNA Deletions
Digenic PEO with mtDNA deletions is a complex genetic disorder, caused by mutations in multiple genes. Research has identified several genes that play a crucial role in the development of this condition, such as thymidine kinase 2 (TK2), OPA1, and POLG2. These genes are involved in maintaining the integrity of mtDNA, which is essential for the proper functioning of the mitochondria, the energy-producing structures within cells.
Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions
This study discovered compound heterozygous mutations in the TK2 gene as a new genetic cause of autosomal recessive PEO with multiple mtDNA deletions. The mutations lead to a deficiency in the TK2 enzyme, which is crucial for the maintenance of mtDNA.
Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance
OPA1 is another gene that plays a significant role in the development of PEO with mtDNA deletions. This research highlights the importance of OPA1 in mtDNA maintenance and its association with diseases involving secondary defects of mtDNA, such as PEO.
Single mitochondrial DNA deletions in chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS) patients from a multiethnic Asian population
This study analyzed single mtDNA deletions in 11 CPEO and one KSS patients, representing the first genetic screen of mtDNA disorders in Malaysia. The findings emphasize the importance of understanding the genetic basis of PEO with mtDNA deletions in diverse populations.
Mutant POLG2 Disrupts DNA Polymerase γ Subunits and Causes Progressive External Ophthalmoplegia
POLG2 is another gene implicated in PEO with mtDNA deletions. This article describes a heterozygous dominant mutation in POLG2, which disrupts the DNA polymerase γ subunits and leads to PEO with multiple mtDNA deletions and cytochrome c oxidase (COX) deficient muscle fibers.
Diagnosing Digenic Progressive External Ophthalmoplegia with mtDNA Deletions
Diagnosing PEO with mtDNA deletions involves a combination of clinical examination, imaging studies, and genetic testing. Clinical examination focuses on the assessment of eye movement and the presence of other neurological symptoms. Imaging studies, such as magnetic resonance imaging (MRI), can provide additional information on the structural changes in the brain and the muscles surrounding the eyes.
Genetic Testing for Digenic Progressive External Ophthalmoplegia with mtDNA Deletions
Genetic testing plays a crucial role in the diagnosis and management of PEO with mtDNA deletions. By identifying the specific gene mutations involved, genetic testing can provide a definitive diagnosis, guide treatment decisions, and offer valuable information for family planning.
Benefits of Genetic Testing
Genetic testing for PEO with mtDNA deletions offers several benefits, including:
- Confirming the diagnosis, especially in cases with atypical or mild symptoms
- Identifying the specific gene mutations, which can help in predicting the disease course and severity
- Providing information on the risk of recurrence in future pregnancies
- Offering the possibility of prenatal or preimplantation genetic diagnosis for couples at risk of having a child with PEO with mtDNA deletions
In conclusion, understanding the genetic basis of digenic PEO with mtDNA deletions is essential for accurate diagnosis and effective management of the disease. Genetic testing offers valuable insights into the specific gene mutations involved, guiding treatment decisions and providing crucial information for family planning.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)