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Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene
Subjects with hypercholesterolemia who do not carry a mutation in the low density lipoprotein receptor gene, in the apolipoprotein B gene or in the proprotein convertase subtilisin/kexin type 9 gene, could possible carry a mutation in the apolipoprotein E (APOE) gene. DNA from 844 unrelated hypercho...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094269/ https://www.ncbi.nlm.nih.gov/pubmed/27830118 http://dx.doi.org/10.1016/j.ymgmr.2016.10.007 |
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author | Leren, Trond P. Strøm, Thea Bismo Berge, Knut Erik |
author_facet | Leren, Trond P. Strøm, Thea Bismo Berge, Knut Erik |
author_sort | Leren, Trond P. |
collection | PubMed |
description | Subjects with hypercholesterolemia who do not carry a mutation in the low density lipoprotein receptor gene, in the apolipoprotein B gene or in the proprotein convertase subtilisin/kexin type 9 gene, could possible carry a mutation in the apolipoprotein E (APOE) gene. DNA from 844 unrelated hypercholesterolemic subjects who did not carry a mutation in any of the three above mentioned genes, was subjected to DNA sequencing of the APOE gene. Two subjects were found to be heterozygous for mutation p.Thr5*. This mutation which generates a stop codon in the signal peptide, is assumed to prevent the synthesis of APOE. Family studies revealed that the mutation was carried on an APOE4 allele in both families. In one of the families only those who had an APOE2 allele as the second allele, had hypercholesterolemia. These were functionally hemizygous for APOE2 and presented with a Type III hyperlipoproteinemia phenotype. However, in the second family, hypercholesterolemia was observed in the index patient who had APOE3 as the second allele, but not in four heterozygous family members who also had APOE3 as the second allele. These findings underscore that the phenotypic expression of mutations in the APOE gene is variable and that the trait exhibits reduced penetrance. |
format | Online Article Text |
id | pubmed-5094269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-50942692016-11-09 Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene Leren, Trond P. Strøm, Thea Bismo Berge, Knut Erik Mol Genet Metab Rep Research Paper Subjects with hypercholesterolemia who do not carry a mutation in the low density lipoprotein receptor gene, in the apolipoprotein B gene or in the proprotein convertase subtilisin/kexin type 9 gene, could possible carry a mutation in the apolipoprotein E (APOE) gene. DNA from 844 unrelated hypercholesterolemic subjects who did not carry a mutation in any of the three above mentioned genes, was subjected to DNA sequencing of the APOE gene. Two subjects were found to be heterozygous for mutation p.Thr5*. This mutation which generates a stop codon in the signal peptide, is assumed to prevent the synthesis of APOE. Family studies revealed that the mutation was carried on an APOE4 allele in both families. In one of the families only those who had an APOE2 allele as the second allele, had hypercholesterolemia. These were functionally hemizygous for APOE2 and presented with a Type III hyperlipoproteinemia phenotype. However, in the second family, hypercholesterolemia was observed in the index patient who had APOE3 as the second allele, but not in four heterozygous family members who also had APOE3 as the second allele. These findings underscore that the phenotypic expression of mutations in the APOE gene is variable and that the trait exhibits reduced penetrance. Elsevier 2016-10-25 /pmc/articles/PMC5094269/ /pubmed/27830118 http://dx.doi.org/10.1016/j.ymgmr.2016.10.007 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Leren, Trond P. Strøm, Thea Bismo Berge, Knut Erik Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene |
title | Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene |
title_full | Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene |
title_fullStr | Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene |
title_full_unstemmed | Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene |
title_short | Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene |
title_sort | variable phenotypic expression of nonsense mutation p.thr5* in the apoe gene |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094269/ https://www.ncbi.nlm.nih.gov/pubmed/27830118 http://dx.doi.org/10.1016/j.ymgmr.2016.10.007 |
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