Case Report: Next-Generation Sequencing Identified a Novel Pair of Compound-Heterozygous Mutations of LPL Gene Causing Lipoprotein Lipase Deficiency

Figures

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  FIGURE 1. Clinical and genetic information of the patient. (A) Pedigree analysis of this family. (B) Blood fractionations (set for 24 h) between control and the patient. (C) Sanger sequencing of variants c.862G>A and c.461A>G with corresponding wild-types. (D) Three-dimensional protein model of lipoprotein lipase. Polar contacts (yellow dash line) between His154 and Arg180 lost and new interactions between His154 and Tyr315 appeared after H154R alteration. With A288T variant, a new repulsion formed between Thr288 and Ile232 (red cylinder). (E) Multiple alignments of LPL protein sequence across 13 species. Mutation sites His154 and Ala288 are labelled by a red rectangular. *in the last row indicates amino acid in this site is “highly conserved”.

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  FIGURE 2. Cholesterol (CHOL) and triglyceride (TG) levels with bezafibrate (BZF) and levocarnitine (LVC) administration. The patient was admitted to hospital with high levels of CHOL (12.58 mmol/L) and TG (67.84 mmol/L) at the age of 3 months and 16 days. Three days later, her CHOL and TG levels plummeted due to bezafibrate and levocarnitine administration. The levels kept decreasing until she was discharged. Her parents reduced the dose without professional medical advice, resulting in a severe relapse (a sharp increased TG level at the age of 6 months and 14 days). The dose of medications was then adjusted and CHOL and TG levels of the patient finally declined to normal and almost normal. (TG: 1 mol/L = 88.5 mg/dl).

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  FIGURE 3. The spectrum landscape of mutations in LPL gene. Lipoprotein lipase (1-475) consists of lipase (17-338) and polycystin-1, lipoxygenase, alpha-toxin or lipoxygenase homology (PLAT/LH2) domain (343-463). A total of 287 mutations and polymorphisms of LPL gene were reported in HGMD. Disease-causing mutations (DMs) are marked in the top. Other non-DMs and polymorphisms are marked in the bottom. Two variants identified in our case are highlighted in red square.