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Diagnosis of Leber’s hereditary optic neuropathy (LHON): analysis of MT-ND1, MT-ND4 and MT-ND6 in patients with LHON
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2009 (Swedish)Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Leber´s hereditary optic neuropathy (LHON), a disease affecting vision, is caused by several point mutations in mitochondrial DNA. Mutations leading to a defect NADH ubiquinone oxidoreductase protein will affect the respiratory chain and cause a disturbed ATP production. It is still unknown why this defect leads to the degeneration of retinal ganglion cells and cells in the opticus nerve as well as demyelination of axons in these areas. Analysis of mitochondrial DNA is an important tool in the diagnosis of the disease. At the present time analysis is based on cleavage by restriction enzymes, which only detects two of the most frequent mutations: m.3460G>A and m.11778G>A. This is far too few considering that more than 30 mutations are known to be associated with LHON. Therefore a new analysis method is requested. Here we describe a method based on the sequencing of the mitochondrial genes MT-ND1, MT-ND4 and MT-ND6, which will detect more than 15 different point mutations associated with the disease. To validate the analysis, DNA from 31 patients with LHON symptoms were sequenced; of these 10 were found to be positive for a LHON mutation. This result indicates that the sequencing analysis will be more effective in diagnosis of LHON than restriction enzymes.

Abstract [sv]

Lebers hereditära optikus neuropati (LHON) är en sjukdom som beror på genetiska förändringar i arvsmassan som leder till att cellens energiomsättning rubbas. Detta gör att nervceller i ögat och synnerven bryts ned vilket leder till en synnedsättning. En patient som drabbas av LHON har inga symptom fram till dess att synen börjar försämras. Sjukdomsförloppet går snabbt och på bara några veckor är patienten ofta helt blind. Diagnostik av LHON idag utgörs av flera undersökningar av öga och synfält. Diagnosen bekräftas av en analys av arvsmassan som finns i mitokondrien, cellens energifabrik. Här beskriver vi en ny förbättrad analysmetod baserad på DNA sekvensering, dvs. bestämning av baserna i mitokondriella arvsmassan. För att utvärdera analysen har vi undersökt 31 patienter med misstänkt LHON - av dessa visade sig 10 bära på en sjuklig förändring. Resultatet visar att sekvensering med fördel kan ersätta den tidigare analysmetoden då fler sjukliga förändringar kan påvisas och utförandet av analysen är mer användarvänligt.

Place, publisher, year, edition, pages
2009. , 16 p.
Keyword [en]
Leber’s hereditary optic neuropathy, LHON, Mitochondrial DNA, Polymorphism, Mutation
Identifiers
URN: urn:nbn:se:uu:diva-109492OAI: oai:DiVA.org:uu-109492DiVA: diva2:272658
Presentation
(English)
Uppsok
Medicine
Supervisors
Examiners
Available from: 2009-10-26 Created: 2009-10-15 Last updated: 2010-07-13Bibliographically approved

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