A Novel Lipoprotein Lipase Mutation in an Infant With Glycogen Storage Disease Type-Ib and Severe Hypertriglyceridemia

Wang, Feng‐Yu; Wang, Fengli; Zhou, Xiangzhi; Yi, Yingjie; Zhao, Jie

doi:10.3389/fped.2021.671536

Cited by 2 publications

(1 citation statement)

References 16 publications

(17 reference statements)

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“…Ages at genetic analysis in these patients, whenever informative, were almost invariably > 20 years. c.483delA represents a notable exception: it was identified in a 5-month-old girl with glycogen storage disease type Ib, and the carrier was found to have severe HTG during laboratory tests in relation to her primary disease [ 42 ]. It is possible that glycogen storage disease type Ib may have precipitated the early-onset occurrence of severe HTG in this particular case.…”

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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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%

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

View full text Add to dashboard Cite

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Three novel SLC37A4 variants in glycogen storage disease type 1b and a literature review

Wang,

Zhao,

Jia

et al. 2023

J Int Med Res

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Glycogen storage disease type 1b (GSD1b) is a rare genetic disorder, resulting from mutations in the SLC37A4 gene located on chromosome 11q23.3. Although the SLC37A4 gene has been identified as the pathogenic gene for GSD1b, the complete variant spectrum of this gene remains to be fully elucidated. In this study, we present three patients diagnosed with GSD1b through genetic testing. We detected five variants of the SLC37A4 gene in these three patients, with three of these mutations (p. L382Pfs*15, p. G117fs*28, and p. T312Sfs*13) being novel variants not previously reported in the literature. We also present a literature review and general overview of the currently reported SLC37A4 gene variants. Our study expands the mutation spectrum of SLC37A4, which may help enable genetic testing to facilitate prompt diagnosis, appropriate intervention, and genetic counseling for affected families.

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A Novel Lipoprotein Lipase Mutation in an Infant With Glycogen Storage Disease Type-Ib and Severe Hypertriglyceridemia

Cited by 2 publications

References 16 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

Three novel SLC37A4 variants in glycogen storage disease type 1b and a literature review

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