Genetic biomarkers can be particularly valuable in the diagnosis of various mitochondrial disorders, aiding in the detection of mitochondrial diseases. The mission of Protheragen is to offer state-of-the-art solutions for the identification and development of genetic biomarkers associated with mitochondrial diseases.
Genetic Biomarkers for Mitochondrial Diseases
Pathogenetic mutations in nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) can impact the structural subunits of the respiratory chain or the machinery responsible for mitochondrial protein synthesis. Numerous point mutations and large-scale rearrangements of DNA have been demonstrated to be causative factors in disease development.
- Mutations in nDNA Related to Mitochondrial Disease
The diagnosis of mitochondrial diseases is further complicated by the often elusive relationship between genotype and observed clinical phenotype; certain nDNA mutations can give rise to multiple distinct clinical syndromes.
| Syndrome |
Genetics |
Clinical Features |
|---|
| Alpers-Huttenlocher syndrome (AHS) |
nDNA (POLG-related) |
Intractable epilepsy, liver, and psychomotor regression disease; might also include the clinical features of MCHS and MEMSA. |
| Sengers syndrome |
nDNA (AGK mutations) |
Congenital cataracts, hypertrophic cardiomyopathy, myopathy, skeletal exercise intolerance and lactic acidosis. Patients can present with or without mtDNA depletion in muscle. |
| MEGDEL syndrome (also known as 3 methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome) |
nDNA (SERAC1 mutations) |
Sensorineural hearing loss, encephalopathy, failure to thrive, psychomotor delay, hypotonia, spasticity, dystonia, hypoglycemia, hepatopathy and lactic acidosis. |
- Mutations in mtDNA Related to Mitochondrial Disease
Mitochondrial diseases are predominantly caused by recessive mutations in nDNA or high levels of heteroplasmic mutations in mtDNA.
| Syndrome |
Genetics |
Clinical Features |
| Pearson syndrome |
Single, large-scale mtDNA deletion or rearrangements of mtDNA (often sporadic) |
Sideroblastic anemia of childhood associated with exocrine and/or endocrine pancreatic dysfunction, pancytopenia, and renal tubulopathy. |
| Leber hereditary optic neuropathy (LHON) |
Mutations in mtDNA, for example, m.11778G>A (MT-ND4), m.14484T>C (MT-ND6) and m.3460G>A (MT-ND1) |
Subacute painless bilateral visual loss. Might also include dystonia, cardiac pre-excitation syndromes, and LHON associated with multiple sclerosis-like symptoms (Harding syndrome). |
| Kearns–Sayre syndrome (KSS) |
Single, large-scale mtDNA deletion (often sporadic) |
PEO, pigmentary retinopathy (progressive vision impairment due to degeneration of the rod photoreceptors), CSF protein levels of >1 g per l, cerebellar ataxia, cardiac conduction abnormalities (age of onset <20 years), myopathy, diabetes mellitus, deafness, bulbar weakness, and dementia. |
| Leigh syndrome |
>75 genes in nDNA and mtDNA |
Acute periods of neurodevelopmental regression followed by partial recovery, hypotonia, dystonia, hypopnoea, dysphagia, epilepsy, failure to thrive, encephalopathy, and basal ganglia and brainstem lesions. |
| Congenital lactic acidosis (CLA) |
nDNA, de novo mtDNA point mutations or inherited mtDNA point mutations |
Childhood-onset, progressive neuromuscular weakness, often fatal, accumulation of lactate in the blood (acidosis), urine and/or CSF. |
Our Services
Due to the wide range of organs and tissues affected by mitochondrial diseases, as well as the presence of various symptoms, diagnosing these conditions can pose a challenge. Protheragen strives to equip researchers with meticulous genetic biomarkers development services and workflows that facilitate early diagnosis, prognosis, and targeted therapeutic interventions.
Sample Collection and Processing
Develop standardized protocols for sample collection to ensure adherence to ethical standards and regulatory requirements.
Utilize advanced genomic technologies for the extraction of high-quality genetic material.
Genomic Analysis
Conduct cutting-edge genomic analysis using state-of-the-art tools to sequence and analyze genetic material.
Employ bioinformatics and data analysis techniques to identify potential biomarkers.
Biomarker Selection
Carefully select validated genetic biomarkers based on their specificity and sensitivity.
Prioritize biomarkers with potential clinical significance.
Validation Studies
Conduct validation studies to confirm the association between identified genetic markers and the targeted disease.
Collaborate with research partners and experts for comprehensive validation.
Assay Development
Develop robust and reproducible assays for the selected biomarkers.
Optimize assay conditions to ensure accuracy and reliability in diagnostic applications.
Our Advantages
Reliable Data and Results
Protheragen is committed to providing customers with high-quality, specialized services to promote scientific research in the field of mitochondrial diseases. If you are interested in our services, please contact us for more detailed information.
