Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis.
<h4>Aims</h4>Genetic factors explain a proportion of the inter-individual variation in the risk for atherosclerotic events, but the genetic basis of atherosclerosis and atherothrombosis in families with Mendelian forms of premature atherosclerosis is incompletely understood. We set out t...
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Public Library of Science (PLoS)
2014-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0098289 |
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| author | Stephanie Maiwald Suthesh Sivapalaratnam Mahdi M Motazacker Julian C van Capelleveen Ilze Bot Saskia C de Jager Miranda van Eck Jennifer Jolley Johan Kuiper Jonathon Stephens Cornelius A Albers C Ruben Vosmeer Heleen Kruize Daan P Geerke Allard C van der Wal Chris M van der Loos John J P Kastelein Mieke D Trip Willem H Ouwehand Geesje M Dallinga-Thie G Kees Hovingh |
| author_facet | Stephanie Maiwald Suthesh Sivapalaratnam Mahdi M Motazacker Julian C van Capelleveen Ilze Bot Saskia C de Jager Miranda van Eck Jennifer Jolley Johan Kuiper Jonathon Stephens Cornelius A Albers C Ruben Vosmeer Heleen Kruize Daan P Geerke Allard C van der Wal Chris M van der Loos John J P Kastelein Mieke D Trip Willem H Ouwehand Geesje M Dallinga-Thie G Kees Hovingh |
| author_sort | Stephanie Maiwald |
| collection | DOAJ |
| description | <h4>Aims</h4>Genetic factors explain a proportion of the inter-individual variation in the risk for atherosclerotic events, but the genetic basis of atherosclerosis and atherothrombosis in families with Mendelian forms of premature atherosclerosis is incompletely understood. We set out to unravel the molecular pathology in a large kindred with an autosomal dominant inherited form of premature atherosclerosis.<h4>Methods and results</h4>Parametric linkage analysis was performed in a pedigree comprising 4 generations, of which a total of 11 members suffered from premature vascular events. A parametric LOD-score of 3.31 was observed for a 4.4 Mb interval on chromosome 12. Upon sequencing, a non-synonymous variant in KERA (c.920C>G; p.Ser307Cys) was identified. The variant was absent from nearly 28,000 individuals, including 2,571 patients with premature atherosclerosis. KERA, a proteoglycan protein, was expressed in lipid-rich areas of human atherosclerotic lesions, but not in healthy arterial specimens. Moreover, KERA expression in plaques was significantly associated with plaque size in a carotid-collar Apoe-/- mice (r2 = 0.69; p<0.0001).<h4>Conclusion</h4>A rare variant in KERA was identified in a large kindred with premature atherosclerosis. The identification of KERA in atherosclerotic plaque specimen in humans and mice lends support to its potential role in atherosclerosis. |
| format | Article |
| id | doaj-art-d0ef6506d4f4491a80ea2afb192bac40 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-d0ef6506d4f4491a80ea2afb192bac402025-08-20T03:46:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9828910.1371/journal.pone.0098289Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis.Stephanie MaiwaldSuthesh SivapalaratnamMahdi M MotazackerJulian C van CapelleveenIlze BotSaskia C de JagerMiranda van EckJennifer JolleyJohan KuiperJonathon StephensCornelius A AlbersC Ruben VosmeerHeleen KruizeDaan P GeerkeAllard C van der WalChris M van der LoosJohn J P KasteleinMieke D TripWillem H OuwehandGeesje M Dallinga-ThieG Kees Hovingh<h4>Aims</h4>Genetic factors explain a proportion of the inter-individual variation in the risk for atherosclerotic events, but the genetic basis of atherosclerosis and atherothrombosis in families with Mendelian forms of premature atherosclerosis is incompletely understood. We set out to unravel the molecular pathology in a large kindred with an autosomal dominant inherited form of premature atherosclerosis.<h4>Methods and results</h4>Parametric linkage analysis was performed in a pedigree comprising 4 generations, of which a total of 11 members suffered from premature vascular events. A parametric LOD-score of 3.31 was observed for a 4.4 Mb interval on chromosome 12. Upon sequencing, a non-synonymous variant in KERA (c.920C>G; p.Ser307Cys) was identified. The variant was absent from nearly 28,000 individuals, including 2,571 patients with premature atherosclerosis. KERA, a proteoglycan protein, was expressed in lipid-rich areas of human atherosclerotic lesions, but not in healthy arterial specimens. Moreover, KERA expression in plaques was significantly associated with plaque size in a carotid-collar Apoe-/- mice (r2 = 0.69; p<0.0001).<h4>Conclusion</h4>A rare variant in KERA was identified in a large kindred with premature atherosclerosis. The identification of KERA in atherosclerotic plaque specimen in humans and mice lends support to its potential role in atherosclerosis.https://doi.org/10.1371/journal.pone.0098289 |
| spellingShingle | Stephanie Maiwald Suthesh Sivapalaratnam Mahdi M Motazacker Julian C van Capelleveen Ilze Bot Saskia C de Jager Miranda van Eck Jennifer Jolley Johan Kuiper Jonathon Stephens Cornelius A Albers C Ruben Vosmeer Heleen Kruize Daan P Geerke Allard C van der Wal Chris M van der Loos John J P Kastelein Mieke D Trip Willem H Ouwehand Geesje M Dallinga-Thie G Kees Hovingh Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis. PLoS ONE |
| title | Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis. |
| title_full | Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis. |
| title_fullStr | Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis. |
| title_full_unstemmed | Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis. |
| title_short | Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis. |
| title_sort | mutation in kera identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis |
| url | https://doi.org/10.1371/journal.pone.0098289 |
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