Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations

Amanda Hooper, G.M. Crawford, J.M. Brisbane, Kenneth Robertson, Gerald Watts, Frank Van Bockxmeer, John Burnett

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was similar to 30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxylterminal 12% of the mature LPL. Trp(394) is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 +/- 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 +/- 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.
Original languageEnglish
Pages (from-to)102-105
JournalAnnals of Clinical Biochemistry
Volume45
DOIs
Publication statusPublished - 2008

Fingerprint

Hyperlipoproteinemia Type I
Lipoprotein Lipase
Genes
Mutation
Triglycerides
Heterozygote
Exons
Nonsense Codon
Hypertriglyceridemia
Missense Mutation
Tryptophan
Plasmas
Lipoproteins
Heparin
Lipids
Amino Acids
Substitution reactions

Cite this

Hooper, Amanda ; Crawford, G.M. ; Brisbane, J.M. ; Robertson, Kenneth ; Watts, Gerald ; Van Bockxmeer, Frank ; Burnett, John. / Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations. In: Annals of Clinical Biochemistry. 2008 ; Vol. 45. pp. 102-105.
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title = "Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations",
abstract = "Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was similar to 30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxylterminal 12{\%} of the mature LPL. Trp(394) is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 +/- 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 +/- 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.",
author = "Amanda Hooper and G.M. Crawford and J.M. Brisbane and Kenneth Robertson and Gerald Watts and {Van Bockxmeer}, Frank and John Burnett",
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Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations. / Hooper, Amanda; Crawford, G.M.; Brisbane, J.M.; Robertson, Kenneth; Watts, Gerald; Van Bockxmeer, Frank; Burnett, John.

In: Annals of Clinical Biochemistry, Vol. 45, 2008, p. 102-105.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations

AU - Hooper, Amanda

AU - Crawford, G.M.

AU - Brisbane, J.M.

AU - Robertson, Kenneth

AU - Watts, Gerald

AU - Van Bockxmeer, Frank

AU - Burnett, John

PY - 2008

Y1 - 2008

N2 - Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was similar to 30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxylterminal 12% of the mature LPL. Trp(394) is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 +/- 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 +/- 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.

AB - Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was similar to 30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxylterminal 12% of the mature LPL. Trp(394) is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 +/- 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 +/- 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.

U2 - 10.1258/acb.2007.007080

DO - 10.1258/acb.2007.007080

M3 - Review article

VL - 45

SP - 102

EP - 105

JO - Annals of Clincal Biochemistry

JF - Annals of Clincal Biochemistry

SN - 0004-5632

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