Identification and functional characterization of mutations in LPL gene causing severe hypertriglyceridaemia and acute pancreatitis

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DOI

  • Peng Han, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Guohong Wei, Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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  • Ke Cai, Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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  • Xi Xiang
  • Wang Ping Deng, Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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  • Yan Bing Li, Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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  • Shan Kuang, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Zhanying Dong, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Tianyu Zheng, BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China.
  • ,
  • Yonglun Luo
  • Junnian Liu, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Yuanning Guan, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Chen Li, Institute of Genetics and Department of Genetics, Zhejiang University School of Medicine, Hangzhou, China.
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  • Subrata Kumar Dey, Brainware university, Barasat, West Bengal, India.
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  • Zhihong Liao, Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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  • Santasree Banerjee, Brainware university, Barasat, West Bengal, India.

Hypertriglyceridaemia is a very rare disorder caused by the mutations of LPL gene, with an autosomal recessive mode of inheritance. Here, we identified two unrelated Chinese patients manifested with severe hypertriglyceridaemia and acute pancreatitis. The clinical symptoms of proband 1 are more severe than proband 2. Whole exome sequencing and Sanger sequencing were performed. Functional analysis of the identified mutations has been done. Whole exome sequencing identified two pairs of variants in LPL gene in the proband 1 (c.162C>A and c.1322+1G>A) and proband 2 (c.835C>G and c.1322+1G>A). The substitution (c.162C>A) leads to the formation of a truncated (p.Cys54*) LPL protein. The substitution (c.835C>G) leads to the replacement of leucine to valine (p.Leu279Val). The splice donor site mutation (c.1322+1G>A) leads to the formation of alternative transcripts with the loss of 134 bp in exon 8 of the LPL gene. The proband 1 and his younger son also harbouring a heterozygous variant (c.553G>T; p.Gly185Cys) in APOA5 gene. The relative expression level of the mutated LPL mRNA (c.162C>A, c.835C>G and c.1322+1G>A) showed significant differences compared to wild-type LPL mRNA, suggesting that all these three mutations affect the transcription of LPL mRNA. These three mutations (c.162C>A, c.835C>G and c.1322+1G>A) showed noticeably decreased LPL activity in cell culture medium but not in cell lysates. Here, we identified three mutations in LPL gene which causes severe hypertriglyceridaemia with acute pancreatitis in Chinese patients. We also described the significance of whole exome sequencing for identifying the candidate gene and disease-causing mutation in patients with severe hypertriglyceridaemia and acute pancreatitis.

Original languageEnglish
JournalJournal of Cellular and Molecular Medicine (Online)
Volume24
Issue2
Pages (from-to)1286-1299
ISSN1582-4934
DOIs
Publication statusPublished - Jan 2020

Bibliographical note

© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

    Research areas

  • LPL gene, acute pancreatitis, compound heterozygous, hypertriglyceridaemia, novel mutations

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