Mitocondrial genes involved in human disease -
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Not only nucleus carry genetic material, even mitocondria do! It plays a very important role in maintaining the genetic variablity and involve in gene expression studies majorly. Mitocondria being a small membrane organelle in each cell perform unique functions as the nuclear DNA does.
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Mitocondrial genes involved in human disease -
- 1. Presenter CHANDANA K MSc SYSTEMS BIOLOGY Manipal school of life science TOPIC FOR THE DAY MITOCHONDRIAL GENES INVOLVED IN HUMAN DISEASES
- 3. INTRODUCTION ETIOLOGY CLINICAL STUDY SYNDROME TYPES OF MITOCHONDRIAL DISEASE DIAGNOSIS TREATMENT DISCUSSION AND CONCLUSON
- 4. 1. WHAT IS MITOCONDRIAL DISEASE? 2. HOW COMMON CHILDHOOD MITOCHONDRIAL DISEASE? 3. HOW COMMON ADULTHOOD MITOCHONDRIAL DISEASE? 4. HOW MANY GENES ARE INFLUENCED IN MITOCONDRIAL DISEASE?
- 5. Powerhouse of the cell Glucose+ oxygen carbon dioxide + water + ATP enzyme Oxidative phosphorylation OXPHOS
- 6. ANY AGE!! • Sporadic • Maternal • Autosomal dominant • Autosomal recessive • X linked INHERITENCE AFFECTS DIFFERENT ORGANS
- 8. It can!
- 10. • Circular DNA, 16,569 bp • 22 tRNAs, 2rRNAs • 13 protein coding genes, and a non coding regions • Maternal inheritance ?? • Lack of introns • Absence of recombination 37 genes 13 genes 24 genes proteins tRNAs rRNAs 22 2 https://www.the-scientist.com/infographics/infographic-- how-the-mitochondrial-and-nuclear-genomes-interact-66625 https://medicalxpress.com/news/2015-01-mitochondrial-dna- mutations-good-bad.html
- 16. Point mutation of mtDNA Nuclear DNA mutation Mitochondrial DNA mutation Single deletion/duplication of mtDNA Mutation of gene related to part of enzyme Mutation of gene related to transportation of mitochondria Mutation of gene related to mitochondrial biogenesis Mutation of gene related to function of mitochondrial DNA Mitochondrial dysfunction = Mitochondrial disease Multiple deletion/duplication of mtDNA Defect of mtDNA https://www.semanticscholar.org/paper/Monogenic-mitochondrial-disorders.-Koopman-Willems/69bf4468535394f9cf38f0cd82cc386844266115/figure/0
- 19. Specific features Threshold effects Mitotic segregation MtDNA bottleneck Clonal expansion 2 1 3 4
- 22. DIAGNOSIS, TREATMENT AND MANAGMENT METABOLIC TESTING GENETIC TESTING MUSCLE TESTING TEST https://bcmj.org/articles/diagnosis-and-management-patients-mitochondrial-disease
- 23. DIAGNOSIS, TREATMENT AND MANAGEMENT cont… TEST https://bcmj.org/articles/diagnosis-and-management-patients-mitochondrial-disease
- 24. DIAGNOSIS, TREATMENT AND MANAGEMENT cont… https://bcmj.org/articles/diagnosis-and-management-patients-mitochondrial-disease
- 25. DIAGNOSIS, TREATMENT AND MANAGEMENT cont.. https://bcmj.org/articles/diagnosis-and-management-patients-mitochondrial-disease
- 26. Mitochondrial disease Type of mutation and gene responsible Age Leigh syndrome Point mutation (mt)m.8993T>C/G,m.10158T>C, m.10191T>C (nuclear genome) SURF1 gene Infancy/adults Kearns –sayre syndrome (KSS) Large scale deletion / reaggangement Later childhood Pearson's syndrome Large scale deletion / reaggangement Early childhood Mitochondrial disease with onset in early infancy / childhood
- 27. Diagnosis • Medical history • Physical examination • Laboratory parameters • MRI/magnetic resonance spectroscopy • Evaluation of findings and primary genetic analysis • Fibroblast culturing and for muscle muscle biopsy • Re-evaluation of findings and genetic diagnosis treatment • Genetic counseling • High doses of biotin and thiamine treatment • Nutraceuticals / vitamin cocktails • Dietary treatment
- 28. DIAGNOSIS • physical examination • Testing of blood and urine samples • Lumbar puncture for CSF analysis • MRI of brain • ECG for detecting heart abnormalities • audiometry and electroretinography • Genetic testing • Muscle biopsy SYMPTOMS • Muscle weakness • Difficulty walking or moving • Dementia, brain damage, or both • Deafness • Heart disease • Short stature (38% of individual) • Small sex organs (20%of individuals) TREATMENT • Coenzyme Q10 • Insulin for diabetes • Cardiac drug • Cardiac pacemaker (life saving). • Surgerical intervention for drooping eyelids
- 29. SYMPTOMS • Sideroblastic anemia • Pancytopenia • Exocrine pancreatic failure DIAGNOSIS AND TREATMENT • Bone marrow examination • Blood testing TREATMENT blood transfusions, • pancreatic enzyme • replacement therapy • treatment of infections Sadly, many children with Pearson syndrome die during infancy.
- 30. Mitochondrial disease Type of mutation and gene responsible Age MELAS Point mutation mtDNA (>80% MTTL1 gene) 2-15 of age CPEO Large scale deletion / reaggangement Point mutation 4 to 40s of age NAPH Point mutation mtDNA (MTND1/MTDN4/MTND8) childhood through early adulthood LHOH Point mutation mt DNA (MTND1/MTND4/MTND6) adolescence or early adulthood /childhood MERRF Point mutation MT-TK childhood or adolescence Mitochondrial disease with onset in late childhood / adult life
- 31. SYMPTOMS - MELAS • Mitocondrial myopathy • Encephalopathy • Lactic Acidosis • Stroke TREATMENT • Metabolic therapies • Anti-convulsant drugs No specific treatment DIAGNOSIS • molecular genetic testing. • Clinical testing lactate and pyruvate concentrations CSF protein
- 32. SYMPTOMS • Ptosis • Ophthalmoplegia TREATMENT • Surgery (ptosis crutch) • Strabismus surgery DIOGNOSIS • Muscle biopsy
- 33. SYMPTOMS • experience numbness • sensory neuropathy • muscle weakness • ataxia • vision loss • Retinitis pigmentosa TREATMENT • Anticonvulsants • Anticognitive therapy DIOGNOSIS • Pathological findings
- 34. DIAGNOSES • genetic test • blood test • Ophthalmologic findings • Physical examination SYMPTOMS • Severe • permanent vision loss • tremors • cardiac defects muscle weakness • coordination and numbness TREATMENT • medical treatment
- 35. DIAGNOSIS • Muscle tissue biopsy • Genetic test SYMPTOMS • Muscle Weakness • Muscle Stiffness • Muscle Twitches • Seizures • Dementia TREATMENT • Coenzyme Q10 and L-carnitine
- 37. DISCUSSION AND CONCLUSION Do mitochondrial disease always comes from mother? Can environmental toxins cause mitochondrial disease? What are the symptoms of a mitochondrial disorder? Why is it important to thoroughly assess the patient before diagnosis? I have heard that muscle biopsy is the definitive test for mitochondrial disease. Is that true? What is the prognosis for children's with mitochondrial disease? Is it true there’s no treatment for mitochondrial disease?
- 38. 1. Chinnery PF. Mitochondrial disease in adults: what's old and what's new? EMBO Mol Med. 2015;7(12);1503-12. 2. Helen A.L. Tuppen, Emma L. Blakely, Douglass M. Turnbull, Robert W. Taylor,Mitochondrial DNA mutations and human disease, Biochimica et Biophysica Acta (BBA) – Bioenergetics.2010; 1797(2);113-128. 3. Thompson K, CollierJJ, Glasgow RIC, et al. Recent advances in understanding the molecular genetic basis of mitochondrial disease. J Inherit Metab Dis. 2020; 43 (1);36-50. 4. Zhou, Bo & Tian, Rong,Mitochondrial dysfunction in pathophysiology of heart failure. Journal of Clinical Investigation. 2018; 128(9);3716–3726.