TY - JOUR
T1 - Incidental finding of severe hypertriglyceridemia in children. Role of multiple rare variants in genes affecting plasma triglyceride
AU - Buonuomo, Paola Sabrina
AU - Rabacchi, Claudio
AU - Macchiaiolo, Marina
AU - Trenti, Chiara
AU - Fasano, Tommaso
AU - Tarugi, Patrizia
AU - Bartuli, Andrea
AU - Bertolini, Stefano
AU - Calandra, Sebastiano
PY - 2017
Y1 - 2017
N2 - Background: The incidental finding of severe hypertriglyceridemia (HyperTG) in a child may suggest the diagnosis of familial chylomicronemia syndrome (FCS), a recessive disorder of the intravascular hydrolysis of triglyceride (TG)-rich lipoproteins. FCS may be due to pathogenic variants in lipoprotein lipase (LPL), as well as 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). Objective: Molecular characterization of 5 subjects in whom HyperTG was an incidental finding during infancy/childhood. Methods: We performed the parallel sequencing of 20 plasma TG-related genes. Results: Three children with severe HyperTG were found to be compound heterozygous for rare pathogenic LPL variants (2 nonsense, 3 missense, and 1 splicing variant). Another child was found to be homozygous for a nonsense variant of APOA5, which was also found in homozygous state in his father with longstanding HyperTG. The fifth patient with a less severe HyperTG was found to be heterozygous for a frameshift variant in LIPC resulting in a truncated Hepatic Lipase. In addition, 1 of the patients with LPL deficiency and the patient with APOA-V deficiency were also heterozygous carriers of a pathogenic variant in LIPC and LPL gene, respectively, whereas the patient with LIPC variant was also a carrier of a rare APOB missense variant. Conclusions: Targeted parallel sequencing of TG-related genes is recommended to define the molecular defect in children presenting with an incidental finding of HyperTG.
AB - Background: The incidental finding of severe hypertriglyceridemia (HyperTG) in a child may suggest the diagnosis of familial chylomicronemia syndrome (FCS), a recessive disorder of the intravascular hydrolysis of triglyceride (TG)-rich lipoproteins. FCS may be due to pathogenic variants in lipoprotein lipase (LPL), as well as 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). Objective: Molecular characterization of 5 subjects in whom HyperTG was an incidental finding during infancy/childhood. Methods: We performed the parallel sequencing of 20 plasma TG-related genes. Results: Three children with severe HyperTG were found to be compound heterozygous for rare pathogenic LPL variants (2 nonsense, 3 missense, and 1 splicing variant). Another child was found to be homozygous for a nonsense variant of APOA5, which was also found in homozygous state in his father with longstanding HyperTG. The fifth patient with a less severe HyperTG was found to be heterozygous for a frameshift variant in LIPC resulting in a truncated Hepatic Lipase. In addition, 1 of the patients with LPL deficiency and the patient with APOA-V deficiency were also heterozygous carriers of a pathogenic variant in LIPC and LPL gene, respectively, whereas the patient with LIPC variant was also a carrier of a rare APOB missense variant. Conclusions: Targeted parallel sequencing of TG-related genes is recommended to define the molecular defect in children presenting with an incidental finding of HyperTG.
KW - APOA5
KW - Familial chylomicronemia
KW - Hypertriglyceridemia
KW - LIPC and APOB genes
KW - LPL
KW - Targeted next-generation sequencing
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U2 - 10.1016/j.jacl.2017.08.017
DO - 10.1016/j.jacl.2017.08.017
M3 - Article
AN - SCOPUS:85029763235
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
SN - 1933-2874
ER -