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Molecular and functional characterisation of Long QT Syndrome causing genes
Thesis (PhD)-- Stellenbosch University, 2014.
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| Format: | Thesis |
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Stellenbosch : Stellenbosch University
2014
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| _version_ | 1867613878120087552 |
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| access_status_str | Open Access |
| author | Hedley, Paula Louise |
| author2 | Corfield, Valerie A. |
| author_browse | Corfield, Valerie A. Hedley, Paula Louise |
| author_facet | Corfield, Valerie A. Hedley, Paula Louise |
| author_sort | Hedley, Paula Louise |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)-- Stellenbosch University, 2014. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/86480 |
| institution | Stellenbosch University (South Africa) |
| last_indexed | 2026-06-10T12:43:08.148Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2014 |
| publishDateRange | 2014 |
| publishDateSort | 2014 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/86480 Molecular and functional characterisation of Long QT Syndrome causing genes Hedley, Paula Louise Corfield, Valerie A. Moolman-Smook, Johanna C. Christiansen, Michael Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division of Molecular Biology and Human Genetics. Long QT syndrome -- Genetic aspects Sudden cardiac death (SCD) -- Genetic aspects Long QT syndrome -- Identification Arrhythmia -- Genetic disorders Theses -- Medicine Theses -- Medical biochemistry Dissertations -- Medicine Dissertations -- Medical biochemistry Myocardial ion channels UCTD Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences Thesis (PhD)-- Stellenbosch University, 2014. ENGLISH ABSTRACT: Ventricular arrhythmias are the most important cause of sudden cardiac death (SCD) among adults living in industrialised nations. Genetic factors have substantial effects in determining population-based risk for SCD and may also account for inter-individual variability in susceptibility. Great progress has been made in identifying genes underlying various Mendelian disorders associated with inherited arrhythmia susceptibility. The most well studied familial arrhythmia syndrome is the congenital long QT syndrome (LQTS) caused by mutations in genes encoding subunits of myocardial ion channels. Not all mutation carriers have equal risk for experiencing the clinical manifestations of disease (i.e. syncope, sudden death). This observation has raised the possibility that additional genetic factors may modify the risk of LQTS manifestations. This study establishes the genetic aetiology of LQTS in South Africa and Denmark through the identification and characterisation of LQTS-causative mutations in five previously identified genes, as well as examining possible novel genetic causes of LQTS in a cohort comprising Danish and British probands. We have functionally characterised several of the mutations identified in this study and examined other cardiac phenotypes that may be explained by variants causing repolarisation disorders. AFRIKAANSE OPSOMMING: Ventrikulêre aritmie bly die enkele belangrikste oorsaak van skielike hart dood (SCD) onder volwassenes wat in geïndustrialiseerde lande woon. Genetiese faktore het aansienlike gevolge in die bepaling van bevolking-gebaseerde risiko vir SCD en kan ook verantwoordelik wees vir die inter-individuele variasie in vatbaarheid. Groot vordering is gemaak in die identifisering van gene onderliggende verskeie Mendeliese siektes wat verband hou met geërf aritmie vatbaarheid. Die mees goed bestudeerde familie aritmie sindroom is die aangebore lang QT-sindroom (LQTS) wat veroorsaak word deur mutasies in gene kode subeenhede van miokardiale ioonkanale. Nie alle mutasie draers het 'n gelyke risiko vir die ervaring van die kliniese manifestasies van die siekte (dws sinkopee, skielike dood). Hierdie waarneming het die moontlikheid genoem dat genetiese faktore anders as die primêre siekte-verwante mutasie kan die risiko van LQTS manifestasies verander. Hierdie studie stel die genetiese oorsake van LQTS in Suid-Afrika en Denemarke deur die identifisering en karakterisering van LQTS-veroorsakende mutasies in vyf voorheen geïdentifiseer gene, asook die behandeling van moontlike nuwe genetiese oorsake van LQTS in 'n groep wat bestaan uit van die Deense en die Britse probands. Ons het funksioneel gekenmerk verskeie van die mutasies wat in hierdie studie ondersoek en ander kardiovaskulêre fenotipes wat deur variante veroorsaak repolarisasie versteurings verduidelik word. South African National Research Foundation Harry and Doris Crossley Foundation Danish Strategic Research Foundation. Doctoral 2014-04-16T17:29:37Z 2014-04-16T17:29:37Z 2014-04 Thesis http://hdl.handle.net/10019.1/86480 Stellenbosch University xix, 213 p. : ill., chiefly col. application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Long QT syndrome -- Genetic aspects Sudden cardiac death (SCD) -- Genetic aspects Long QT syndrome -- Identification Arrhythmia -- Genetic disorders Theses -- Medicine Theses -- Medical biochemistry Dissertations -- Medicine Dissertations -- Medical biochemistry Myocardial ion channels UCTD Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences Hedley, Paula Louise Molecular and functional characterisation of Long QT Syndrome causing genes |
| title | Molecular and functional characterisation of Long QT Syndrome causing genes |
| title_full | Molecular and functional characterisation of Long QT Syndrome causing genes |
| title_fullStr | Molecular and functional characterisation of Long QT Syndrome causing genes |
| title_full_unstemmed | Molecular and functional characterisation of Long QT Syndrome causing genes |
| title_short | Molecular and functional characterisation of Long QT Syndrome causing genes |
| title_sort | molecular and functional characterisation of long qt syndrome causing genes |
| topic | Long QT syndrome -- Genetic aspects Sudden cardiac death (SCD) -- Genetic aspects Long QT syndrome -- Identification Arrhythmia -- Genetic disorders Theses -- Medicine Theses -- Medical biochemistry Dissertations -- Medicine Dissertations -- Medical biochemistry Myocardial ion channels UCTD Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences |
| url | http://hdl.handle.net/10019.1/86480 |
| work_keys_str_mv | AT hedleypaulalouise molecularandfunctionalcharacterisationoflongqtsyndromecausinggenes |