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Mitochondrial DNA (mtDNA) mutations in patients with suspected myoclonic epilepsy and ragged red muscle fibres (MERRF), Leigh syndrome (LS), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)
Dissertation (MSc (Human Genetics))--University of Pretoria, 2007.
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University of Pretoria
2013
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| _version_ | 1867613457999724544 |
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| access_status_str | Open Access |
| author2 | Olckers, Antonel |
| author_browse | Olckers, Antonel |
| author_facet | Olckers, Antonel |
| collection | Thesis |
| dc_rights_str_mv | © 2001, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Dissertation (MSc (Human Genetics))--University of Pretoria, 2007. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/30471 |
| institution | University of Pretoria (South Africa) |
| last_indexed | 2026-06-10T12:36:27.633Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2013 |
| publishDateRange | 2013 |
| publishDateSort | 2013 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/30471 Mitochondrial DNA (mtDNA) mutations in patients with suspected myoclonic epilepsy and ragged red muscle fibres (MERRF), Leigh syndrome (LS), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) Olckers, Antonel upetd@up.ac.za Smuts, Izelle Prosser, Debra Olive Mitochondrial encephalomyopathy Spasms infantile Mitochondrial pathology Leigh syndrome Lactic acidosis UCTD Dissertation (MSc (Human Genetics))--University of Pretoria, 2007. Mitochondrial disorders are considered to be the most common cause of metabolic abnormalities in the paediatric neurology population (Zeviani et al., 1996). These authors reported that the phenotypes observed in 25-30% of the paediatric patients in their neurology clinics were due to a mitochondrial aetiology. The genetic aetiology in an equivalently affected paediatric population in South Africa is currently unknown. This study investigated the possibility that reported mutations could account for the mitochondrial phenotypes observed in the South African population. It focussed on the most frequent paediatric mitochondrial disorders namely: Leigh Syndrome (LS), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and myoclonic epilepsy and ragged red muscle fibres (MERRF). A clinically well characterised group of 25 patients with mitochondrial disorders was included in this study. The molecular analysis of the mitochondrial genome was initially based on a restriction fragment length polymorphism (RFLP) screening strategy for the ten most common mitochondrial DNA (mtDNA) mutations associated with the above¬mentioned three disorders. However, during the study the mutation analysis strategy was modified to a sequencing strategy as this provided more information than the RFLP approach. The modified sequencing strategy extended the study to incorporate fifteen additional mtDNA mutations, associated with other mitochondrial disorders, and individuals included in the study were thus investigated for the presence of 25 mtDNA mutations. Moreover, the modified strategy provided additional information of the regions encompassing the reported mutations. A single patient was observed to harbour the reported A3243G MELAS mutation. This mutation was noted to be heteroplasmic in the proband and two of her maternal relatives. None of the other 24 reported mutations were observed in this patient population. One novel mtDNA alteration in the tRNALeu(UUR) gene was observed in a single patient, although the pathogenicity of this mutation remains to be investigated. Novel and reported polymorph isms, some of which are associated with specific haplogroups, were also observed when comparing sequencing data against the Cambridge reference sequence. The data generated during this study contributed towards the understanding of the uniqueness of the South African population in the global context. This was apparent from the fact that only one of the reported mutations was observed in our patient population who were clinically well characterised and displayed phenotypes similar to those reported internationally. Results form this study underlined the complexity of mitochondrial disorders and argues in favour of whole mitochondrial genome sequence information to be used for diagnostic purposes. Moreover, the results confer with the hypothesis that novel mitochondrial mutations may account for the majority of mitochondrial phenotypes observed in the South African population. Genetics unrestricted 2013-09-07T19:09:27Z 2006-01-09 2013-09-07T19:09:27Z 2001-11-01 2007-01-09 2005-12-21 Dissertation Prosser, DO 2001, Mitochondrial DNA (mtDNA) mutations in patients with suspected myoclonic epilepsy and ragged red muscle fibres (MERRF), Leigh syndrome (LS), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://hdl.handle.net/2263/30471 > H510/ag http://hdl.handle.net/2263/30471 http://upetd.up.ac.za/thesis/available/etd-12212005-091637/ © 2001, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | Mitochondrial encephalomyopathy Spasms infantile Mitochondrial pathology Leigh syndrome Lactic acidosis UCTD Mitochondrial DNA (mtDNA) mutations in patients with suspected myoclonic epilepsy and ragged red muscle fibres (MERRF), Leigh syndrome (LS), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) |
| title | Mitochondrial DNA (mtDNA) mutations in patients with suspected myoclonic epilepsy and ragged red muscle fibres (MERRF), Leigh syndrome (LS), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) |
| title_full | Mitochondrial DNA (mtDNA) mutations in patients with suspected myoclonic epilepsy and ragged red muscle fibres (MERRF), Leigh syndrome (LS), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) |
| title_fullStr | Mitochondrial DNA (mtDNA) mutations in patients with suspected myoclonic epilepsy and ragged red muscle fibres (MERRF), Leigh syndrome (LS), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) |
| title_full_unstemmed | Mitochondrial DNA (mtDNA) mutations in patients with suspected myoclonic epilepsy and ragged red muscle fibres (MERRF), Leigh syndrome (LS), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) |
| title_short | Mitochondrial DNA (mtDNA) mutations in patients with suspected myoclonic epilepsy and ragged red muscle fibres (MERRF), Leigh syndrome (LS), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) |
| title_sort | mitochondrial dna mtdna mutations in patients with suspected myoclonic epilepsy and ragged red muscle fibres merrf leigh syndrome ls and mitochondrial encephalomyopathy lactic acidosis and stroke like episodes melas |
| topic | Mitochondrial encephalomyopathy Spasms infantile Mitochondrial pathology Leigh syndrome Lactic acidosis UCTD |
| url | http://hdl.handle.net/2263/30471 http://upetd.up.ac.za/thesis/available/etd-12212005-091637/ |