Dataset Information

Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene.

ABSTRACT: 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.

SUBMITTER: Leren TP

PROVIDER: S-EPMC5094269 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene.

Leren Trond P TP Strøm Thea Bismo TB Berge Knut Erik KE

Molecular genetics and metabolism reports 20161025

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 ...[more]

PMID: 27830118

Similar Datasets

Project description:BackgroundThe degree by which mechanisms underlying phenotypic convergence are similar among taxa depends on the number of evolutionary paths available for selection to act upon. Likelihood of convergence will be influenced by an interplay of factors such as genetic architecture, phylogenetic history and population demography. To determine if there is convergence or divergence in mechanisms underlying phenotypic similarity, we assessed whether gene transcription patterns differed among species with similar levels of hypoxia tolerance.ResultsThree species of marine fish from the superfamily Cottoidea (smoothhead sculpin [Artedius lateralis], sailfin sculpin [Nautichthys oculofasciatus] and Pacific staghorn sculpin [Leptocottus armatus]), all of which have previously been shown to share the same level of hypoxia tolerance, were exposed to short-(8 h) and longer-term (72 h) hypoxia and mRNA transcripts were assessed using a custom microarray. We examined hypoxia-induced transcription patterns in metabolic and protein production pathways and found that a high proportion of genes associated with these biological processes showed significant differences among the species. Specifically, the data suggest that the smoothhead sculpin, unlike the sailfin sculpin and the Pacific staghorn sculpin, relied on amino acid degradation rather than glycolysis or fatty acid oxidation to generate ATP during hypoxia exposure. There was also variation across the species in the transcription of genes involved in protein production (e.g. mRNA processing and protein translation), such that it increased in the smoothhead sculpin, decreased in the sailfin sculpin and was variable in the Pacific staghorn sculpin.ConclusionsChanges in metabolic and protein production pathways are part of the key responses of fishes to exposures to environmental hypoxia. Yet, species with similar overall hypoxia tolerance exhibited different transcriptional responses in these pathways, indicating flexibility and complexity of interactions in the evolution of the mechanisms underlying the hypoxia tolerance phenotype. The variation in the hypoxia-induced transcription of genes across species with similar hypoxia tolerance suggests that similar whole-animal phenotypes can emerge from divergent evolutionary paths that may affect metabolically important functions.

Dataset Information

Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene.

Publications

Variable phenotypic expression of nonsense mutation p.Thr5* in the APOE gene.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets