A novel frameshift mutation in exon 6 (the site of Asn 291) of the lipoprotein lipase gene in type I hyperlipidemia

Kobayashi, Junji; Nagashima, Izumi; Taira, Kouichi; Hikita, Minoru; Tamura, Ken; Bujo, Hideaki; Morisaki, Naho; Saitō, Yasushi

doi:10.1016/s0009-8981(99)00060-1

Cited by 7 publications

(3 citation statements)

References 18 publications

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“… Abbreviations : AP acute pancreatitis, HTG hypertriglyceridemia LPL lipoprotein lipase, M months, NI not informative, TG triglyceride, Y years a For variants that were either not described at the coding DNA reference sequence level or described at the coding DNA reference sequence level but the nomenclature did not follow the current Human Genome Variation Society (HGVS) recommendations b Functional effect refers to the experimentally determined LPL activity (in the medium of transfected cells) of the trans -inherited LPL missense variant relative to that of wild-type LPL c Not informative in the original publication d Described only at the protein level in the first report [ 24 ]. The change at the coding DNA sequence level was obtained from subsequent citing publications [ 57 , 58 ] e Described as Gly188Glu in the original report [ 28 ] f Full text of the original report could not be accessed g Described as a 4 bp deletion (ACTA) in exon 4 in the original report [ 34 ] h Described as Leu286Pro in the original report [ 36 ] i Described as LPL p.Ile194Thr in the original report [ 50 ] …”

Section: Resultsmentioning

confidence: 99%

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Frameshift coding sequence variants in the LPL gene: identification of two novel events and exploration of the genotype–phenotype relationship for variants reported to date

Zhang,

Hu,

Yang

et al. 2023

Lipids Health Dis

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Background Lipoprotein lipase (LPL) is the rate-limiting enzyme for triglyceride hydrolysis. Homozygous or compound heterozygous LPL variants cause autosomal recessive familial chylomicronemia syndrome (FCS), whereas simple heterozygous LPL variants are associated with hypertriglyceridemia (HTG) and HTG-related disorders. LPL frameshift coding sequence variants usually cause complete functional loss of the affected allele, thereby allowing exploration of the impact of different levels of LPL function in human disease. Methods All exons and flanking intronic regions of LPL were Sanger sequenced in patients with HTG-related acute pancreatitis (HTG-AP) or HTG-AP in pregnancy. Previously reported LPL frameshift coding sequence variants were collated from the Human Gene Mutation Database and through PubMed keyword searching. Original reports were manually evaluated for the following information: zygosity status of the variant, plasma LPL activity of the variant carrier, disease referred for genetic analysis, patient’s age at genetic analysis, and patient’s disease history. SpliceAI was employed to predict the potential impact of collated variants on splicing. Results Two novel rare variants were identified, and 53 known LPL frameshift coding sequence variants were collated. Of the 51 variants informative for zygosity, 30 were simple heterozygotes, 12 were homozygotes, and 9 were compound heterozygotes. Careful evaluation of the 55 variants with respect to their clinical and genetic data generated several interesting findings. First, we conclude that 6–7% residual LPL function could significantly delay the age of onset of FCS and reduce the prevalence of FCS-associated syndromes. Second, whereas a large majority of LPL frameshift coding sequence variants completely disrupt gene function through their "frameshift" nature, a small fraction of these variants may act wholly or partly as "in-frame" variants, leading to the generation of protein products with some residual LPL function. Third, we identified two candidate LPL frameshift coding sequence variants that may retain residual function based on genotype–phenotype correlation or SpliceAI-predicted data. Conclusions This study reported two novel LPL variants and yielded new insights into the genotype–phenotype relationship as it pertains to LPL frameshift coding sequence variants.

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Section: Resultsmentioning

confidence: 99%

“…c.953del and p.Ile221Thr: the male carrier of these variants exhibited a relatively mild clinical phenotype compared to typical FCS [ 50 ]. First, he was genetically tested for severe HTG at the age of 33, having not previously reported any other symptoms of FCS.…”

Section: Resultsmentioning

confidence: 99%

Frameshift coding sequence variants in the LPL gene: identification of two novel events and exploration of the genotype–phenotype relationship for variants reported to date

Zhang,

Hu,

Yang

et al. 2023

Lipids Health Dis

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“…The most extensively studied ligands for PPARs are thiazolidinediones (TZDs), a class of drugs used to increase insulin sensitivity. TZDs can decrease insulin resistance, modify adipocyte differentiation, and induce lipoprotein lipase (LPL) by regulating the expression of PPARγ target genes [ 124 , 125 , 126 , 127 ]. However, TZDs are clinically limited due to severe adverse effects, such as fluid retention, weight gain, liver toxicity, and cardiovascular disease [ 38 , 128 , 129 ].…”

Section: Nuclear Receptors As Drug Targets In Related Disease Signmentioning

confidence: 99%

Targeting Nuclear Receptors with Marine Natural Products

Yang

2014

Marine Drugs

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Nuclear receptors (NRs) are important pharmaceutical targets because they are key regulators of many metabolic and inflammatory diseases, including diabetes, dyslipidemia, cirrhosis, and fibrosis. As ligands play a pivotal role in modulating nuclear receptor activity, the discovery of novel ligands for nuclear receptors represents an interesting and promising therapeutic approach. The search for novel NR agonists and antagonists with enhanced selectivities prompted the exploration of the extraordinary chemical diversity associated with natural products. Recent studies involving nuclear receptors have disclosed a number of natural products as nuclear receptor ligands, serving to re-emphasize the translational possibilities of natural products in drug discovery. In this review, the natural ligands of nuclear receptors will be described with an emphasis on their mechanisms of action and their therapeutic potentials, as well as on strategies to determine potential marine natural products as nuclear receptor modulators.

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Lpl-C310R mutation is associated with impaired glucose tolerance and endoplasmic reticulum stress in skeletal muscle

Yue

Sun

Che

et al. 2020

Biochemical and Biophysical Research Communications

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A novel frameshift mutation in exon 6 (the site of Asn 291) of the lipoprotein lipase gene in type I hyperlipidemia

Cited by 7 publications

References 18 publications

Frameshift coding sequence variants in the LPL gene: identification of two novel events and exploration of the genotype–phenotype relationship for variants reported to date

Frameshift coding sequence variants in the LPL gene: identification of two novel events and exploration of the genotype–phenotype relationship for variants reported to date

Targeting Nuclear Receptors with Marine Natural Products

Lpl-C310R mutation is associated with impaired glucose tolerance and endoplasmic reticulum stress in skeletal muscle

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