BACKGROUND: Familial chylomicronemia is a recessive disorder that may be due to mutations in lipoprotein lipase (LPL) and in other proteins such as apolipoprotein C-II and apolipoprotein A-V (activators of LPL), GPIHBP1 (the molecular platform required for LPL activity on endothelial surface), and LMF1 (a factor required for intracellular formation of active LPL). METHODS: We sequenced the familial chylomicronemia candidate genes in 2 adult females presenting long-standing hypertriglyceridemia and a history of acute pancreatitis. RESULTS: Both probands had plasma triglyceride .10 mmol/L but no mutations in the LPL gene. The sequence of the other candidate genes showed that one patient was homozygous for a novel missense mutation p.(Cys83Arg), and the other was homozygous for a previously reported nonsense mutation p.(Cys 89*), respectively, in GPIHBP1. Family screening showed that the hypertriglyceridemic brother of the p.(Cys83Arg) homozygote was also homozygous for this mutation. He had no history of pancreatitis. The p.(Cys83Arg) heterozygous carriers had normal triglyceride levels. The substitution of a cysteine residue in the Ly6 domain of GPIHBP1 is predicted to abolish one of the disulfide bridges required to maintain the structure of GPIHBP1. The p.(Cys89*) mutation results in a truncated protein devoid of function. CONCLUSIONS: Both mutant GPIHBP1 proteins are expected to be incapable of transferring LPL from the subendothelial space to the endothelial surface.

Clinical and genetic features of 3 patients with familial chylomicronemia due to mutations in GPIHBP1 gene / Rabacchi, Claudio; D'Addato, Sergio; Palmisano, Silvia; Lucchi, Tiziano; Bertolini, Stefano; Calandra Buonaura, Sebastiano; Tarugi, Patrizia Maria. - In: JOURNAL OF CLINICAL LIPIDOLOGY. - ISSN 1933-2874. - STAMPA. - 10:4(2016), pp. 915-921.e4. [10.1016/j.jacl.2016.03.009]

Clinical and genetic features of 3 patients with familial chylomicronemia due to mutations in GPIHBP1 gene

RABACCHI, CLAUDIO;CALANDRA BUONAURA, Sebastiano;TARUGI, Patrizia Maria
2016

Abstract

BACKGROUND: Familial chylomicronemia is a recessive disorder that may be due to mutations in lipoprotein lipase (LPL) and in other proteins such as apolipoprotein C-II and apolipoprotein A-V (activators of LPL), GPIHBP1 (the molecular platform required for LPL activity on endothelial surface), and LMF1 (a factor required for intracellular formation of active LPL). METHODS: We sequenced the familial chylomicronemia candidate genes in 2 adult females presenting long-standing hypertriglyceridemia and a history of acute pancreatitis. RESULTS: Both probands had plasma triglyceride .10 mmol/L but no mutations in the LPL gene. The sequence of the other candidate genes showed that one patient was homozygous for a novel missense mutation p.(Cys83Arg), and the other was homozygous for a previously reported nonsense mutation p.(Cys 89*), respectively, in GPIHBP1. Family screening showed that the hypertriglyceridemic brother of the p.(Cys83Arg) homozygote was also homozygous for this mutation. He had no history of pancreatitis. The p.(Cys83Arg) heterozygous carriers had normal triglyceride levels. The substitution of a cysteine residue in the Ly6 domain of GPIHBP1 is predicted to abolish one of the disulfide bridges required to maintain the structure of GPIHBP1. The p.(Cys89*) mutation results in a truncated protein devoid of function. CONCLUSIONS: Both mutant GPIHBP1 proteins are expected to be incapable of transferring LPL from the subendothelial space to the endothelial surface.
2016
23-mar-2016
10
4
915
921.e4
Clinical and genetic features of 3 patients with familial chylomicronemia due to mutations in GPIHBP1 gene / Rabacchi, Claudio; D'Addato, Sergio; Palmisano, Silvia; Lucchi, Tiziano; Bertolini, Stefano; Calandra Buonaura, Sebastiano; Tarugi, Patrizia Maria. - In: JOURNAL OF CLINICAL LIPIDOLOGY. - ISSN 1933-2874. - STAMPA. - 10:4(2016), pp. 915-921.e4. [10.1016/j.jacl.2016.03.009]
Rabacchi, Claudio; D'Addato, Sergio; Palmisano, Silvia; Lucchi, Tiziano; Bertolini, Stefano; Calandra Buonaura, Sebastiano; Tarugi, Patrizia Maria
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1126215
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