Genetic mapping of retinal degenerations in Northern Sweden
Inherited retinal degenerations are a group of disorders characterised by great genetic heterogeneity. Clinically, they can be divided into two large groups of diseases, those associated with night blindness, e.g. retinitis pigmentosa (RP), and those with macular malfunction, e.g. cone/cone-rod dyst...
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Medicinsk och klinisk genetik
2009
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ftumeauniv:oai:DiVA.org:umu-27004 2023-10-09T21:54:30+02:00 Genetic mapping of retinal degenerations in Northern Sweden Köhn, Linda 2009 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-27004 eng eng Medicinsk och klinisk genetik Umeå : Umeå university Umeå University medical dissertations, 0346-6612 1305 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-27004 urn:isbn:978-91-7264-887-6 info:eu-repo/semantics/openAccess Bothnia dystrophy cone dustrophy linkage analysis mutation PITPNM3 PRPF31 retinitis pigmentosa RLBP1 Medical Genetics Medicinsk genetik Doctoral thesis, comprehensive summary info:eu-repo/semantics/doctoralThesis text 2009 ftumeauniv 2023-09-22T13:47:56Z Inherited retinal degenerations are a group of disorders characterised by great genetic heterogeneity. Clinically, they can be divided into two large groups of diseases, those associated with night blindness, e.g. retinitis pigmentosa (RP), and those with macular malfunction, e.g. cone/cone-rod dystrophy (COD/CORD). This thesis is focused on finding the genetic basis of disease in families with autosomal dominant COD, autosomal dominant RP, and Bothnia dystrophy (BD), a regional variant of RP. A variant of COD was previously mapped to 17p12-p13 in a family from northern Sweden. One additional family originating from the same geographical area was included in fine mapping of this chromosome region. Using 12 microsatellite markers in linkage and haplotype analysis, the region was refined from 26.9 to 14.3 cM. A missense mutation, Q626H, in an evolutionarily conserved region of PITPNM3, phosphatidylinositol transfer membrane-associated protein, was identified. The mutation segregated with the disease in both families and was absent from normal control chromosomes. PITPNM3 is a human homologue of the Drosophila retinal degeneration (rdgB) protein, which is highly expressed in the retina and has been proposed to be required for membrane turnover of photoreceptor cells. With the intention of establishing the global impact that PITPNM3 has on retinal degenerations 165 DNA samples from COD and CORD patients were obtained from Denmark, Germany, the UK, and USA and screened for mutations. The Q626H mutation found in the Swedish families was also found in one British family and a novel Q342P variant was detected in a German patient. In addition, two intronic variants were identified: c.900+60C>T and c.901-45G>A. Thus, we concluded that mutations in PITPNM3 represent a rare cause of COD worldwide. In two large families from northern Sweden showing autosomal dominant RP with reduced penetrance, the disease locus was mapped using genome-wide linkage analysis to 19q13.42 (RP11). Since mutation screening of eight genes on ... Doctoral or Postdoctoral Thesis Northern Sweden Umeå University: Publications (DiVA) |
institution |
Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Bothnia dystrophy cone dustrophy linkage analysis mutation PITPNM3 PRPF31 retinitis pigmentosa RLBP1 Medical Genetics Medicinsk genetik |
spellingShingle |
Bothnia dystrophy cone dustrophy linkage analysis mutation PITPNM3 PRPF31 retinitis pigmentosa RLBP1 Medical Genetics Medicinsk genetik Köhn, Linda Genetic mapping of retinal degenerations in Northern Sweden |
topic_facet |
Bothnia dystrophy cone dustrophy linkage analysis mutation PITPNM3 PRPF31 retinitis pigmentosa RLBP1 Medical Genetics Medicinsk genetik |
description |
Inherited retinal degenerations are a group of disorders characterised by great genetic heterogeneity. Clinically, they can be divided into two large groups of diseases, those associated with night blindness, e.g. retinitis pigmentosa (RP), and those with macular malfunction, e.g. cone/cone-rod dystrophy (COD/CORD). This thesis is focused on finding the genetic basis of disease in families with autosomal dominant COD, autosomal dominant RP, and Bothnia dystrophy (BD), a regional variant of RP. A variant of COD was previously mapped to 17p12-p13 in a family from northern Sweden. One additional family originating from the same geographical area was included in fine mapping of this chromosome region. Using 12 microsatellite markers in linkage and haplotype analysis, the region was refined from 26.9 to 14.3 cM. A missense mutation, Q626H, in an evolutionarily conserved region of PITPNM3, phosphatidylinositol transfer membrane-associated protein, was identified. The mutation segregated with the disease in both families and was absent from normal control chromosomes. PITPNM3 is a human homologue of the Drosophila retinal degeneration (rdgB) protein, which is highly expressed in the retina and has been proposed to be required for membrane turnover of photoreceptor cells. With the intention of establishing the global impact that PITPNM3 has on retinal degenerations 165 DNA samples from COD and CORD patients were obtained from Denmark, Germany, the UK, and USA and screened for mutations. The Q626H mutation found in the Swedish families was also found in one British family and a novel Q342P variant was detected in a German patient. In addition, two intronic variants were identified: c.900+60C>T and c.901-45G>A. Thus, we concluded that mutations in PITPNM3 represent a rare cause of COD worldwide. In two large families from northern Sweden showing autosomal dominant RP with reduced penetrance, the disease locus was mapped using genome-wide linkage analysis to 19q13.42 (RP11). Since mutation screening of eight genes on ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Köhn, Linda |
author_facet |
Köhn, Linda |
author_sort |
Köhn, Linda |
title |
Genetic mapping of retinal degenerations in Northern Sweden |
title_short |
Genetic mapping of retinal degenerations in Northern Sweden |
title_full |
Genetic mapping of retinal degenerations in Northern Sweden |
title_fullStr |
Genetic mapping of retinal degenerations in Northern Sweden |
title_full_unstemmed |
Genetic mapping of retinal degenerations in Northern Sweden |
title_sort |
genetic mapping of retinal degenerations in northern sweden |
publisher |
Medicinsk och klinisk genetik |
publishDate |
2009 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-27004 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Umeå University medical dissertations, 0346-6612 1305 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-27004 urn:isbn:978-91-7264-887-6 |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1779318080377192448 |