Molecular basis of the familial chylomicronemia syndrome in patients from the National Dyslipidemia Registry of the Spanish Atherosclerosis Society. Ariza, M. J., Rioja, J., Ibarretxe, D., Camacho, A., Díaz-Díaz, J. L., Mangas, A., Carbayo-Herencia, J. A., Ruiz-Ocaña, P., Lamíquiz-Moneo, I., Mosquera, D., Sáenz, P., Masana, L., Muñiz-Grijalvo, O., Pérez-Calahorra, S., Valdivielso, P., & Spanish Dyslipidemia Registry Journal of Clinical Lipidology, August, 2018. doi abstract bibtex BACKGROUND: Familial chylomicronemia syndrome (FCS) is an extremely rare lipoprotein disorder caused by mutations in at least 5 genes of the lipoprotein lipase (LPL) complex. OBJECTIVE: This work shows the molecular analysis of patients diagnosed with FCS, who attended the Spanish Arteriosclerosis Society lipid units and were included in the National Dyslipidemia Registry. METHODS: Among the 238 patients registered with severe hypertriglyceridemia (fasting triglycerides \textgreater1000 mg/dL), 26 were diagnosed with FCS as they had confirmed postheparin plasma LPL activity deficiency and/or homozygosity for loss-of-function mutations in LPL, GPIHBP1, APOC2, LMF1, or Apolipoprotein A5 (APOA5). RESULTS: Among the 26 FCS cases, 23 had mutations in the homozygous state: 19 in LPL and 4 in the GPIHBP1 gene. The molecular analysis revealed 3 novel mutations: 2 in LPL, in 2 unrelated patients (c.312delA; p.Asp105Thrfs*66 and c.629A\textgreaterG; p.His210Arg), and 1 in GPHIBP1 in a third patient (c.502delC; p.Leu168Serfs*83). These 3 patients had confirmed lack of LPL activity. Three additional patients with confirmed LPL activity deficiency were heterozygous carriers of mutations in the genes analyzed. Among these, we found 2 novel mutations in APOA5 (c.50-1G\textgreaterA and c.326_327insC; p.Tyr110Leufs*158). CONCLUSION: We have identified 5 novel pathogenic mutations: 2 in LPL, 1 in GPIHBP1, and 2 in the APOA5 gene. The genetic defaults accounting for the LPL activity deficiency of 23 of them have been clearly identified and 3 patients, who harbored mutations in heterozygosity, were diagnosed based on LPL activity deficiency, which raises the question of the involvement of new genes in the manifestation of FCS.
@article{ariza_molecular_2018,
title = {Molecular basis of the familial chylomicronemia syndrome in patients from the {National} {Dyslipidemia} {Registry} of the {Spanish} {Atherosclerosis} {Society}},
issn = {1933-2874},
doi = {10.1016/j.jacl.2018.07.013},
abstract = {BACKGROUND: Familial chylomicronemia syndrome (FCS) is an extremely rare lipoprotein disorder caused by mutations in at least 5 genes of the lipoprotein lipase (LPL) complex.
OBJECTIVE: This work shows the molecular analysis of patients diagnosed with FCS, who attended the Spanish Arteriosclerosis Society lipid units and were included in the National Dyslipidemia Registry.
METHODS: Among the 238 patients registered with severe hypertriglyceridemia (fasting triglycerides {\textgreater}1000 mg/dL), 26 were diagnosed with FCS as they had confirmed postheparin plasma LPL activity deficiency and/or homozygosity for loss-of-function mutations in LPL, GPIHBP1, APOC2, LMF1, or Apolipoprotein A5 (APOA5).
RESULTS: Among the 26 FCS cases, 23 had mutations in the homozygous state: 19 in LPL and 4 in the GPIHBP1 gene. The molecular analysis revealed 3 novel mutations: 2 in LPL, in 2 unrelated patients (c.312delA; p.Asp105Thrfs*66 and c.629A{\textgreater}G; p.His210Arg), and 1 in GPHIBP1 in a third patient (c.502delC; p.Leu168Serfs*83). These 3 patients had confirmed lack of LPL activity. Three additional patients with confirmed LPL activity deficiency were heterozygous carriers of mutations in the genes analyzed. Among these, we found 2 novel mutations in APOA5 (c.50-1G{\textgreater}A and c.326\_327insC; p.Tyr110Leufs*158).
CONCLUSION: We have identified 5 novel pathogenic mutations: 2 in LPL, 1 in GPIHBP1, and 2 in the APOA5 gene. The genetic defaults accounting for the LPL activity deficiency of 23 of them have been clearly identified and 3 patients, who harbored mutations in heterozygosity, were diagnosed based on LPL activity deficiency, which raises the question of the involvement of new genes in the manifestation of FCS.},
language = {eng},
journal = {Journal of Clinical Lipidology},
author = {Ariza, María José and Rioja, José and Ibarretxe, Daiana and Camacho, Ana and Díaz-Díaz, José Luis and Mangas, Alipio and Carbayo-Herencia, Julio A. and Ruiz-Ocaña, Pablo and Lamíquiz-Moneo, Itziar and Mosquera, Daniel and Sáenz, Pedro and Masana, Luis and Muñiz-Grijalvo, Ovidio and Pérez-Calahorra, Sofía and Valdivielso, Pedro and {Spanish Dyslipidemia Registry}},
month = aug,
year = {2018},
pmid = {30150141},
keywords = {Article, Candidate genes, Causative mutation, Familial chylomicronemia syndrome, LPL activity, LPL mass, Medicina Interna},
}
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{"_id":"cYW9wBwCFGYvCQy4P","bibbaseid":"ariza-rioja-ibarretxe-camacho-dazdaz-mangas-carbayoherencia-ruizocaa-etal-molecularbasisofthefamilialchylomicronemiasyndromeinpatientsfromthenationaldyslipidemiaregistryofthespanishatherosclerosissociety-2018","downloads":0,"creationDate":"2018-10-09T14:45:41.718Z","title":"Molecular basis of the familial chylomicronemia syndrome in patients from the National Dyslipidemia Registry of the Spanish Atherosclerosis Society","author_short":["Ariza, M. J.","Rioja, J.","Ibarretxe, D.","Camacho, A.","Díaz-Díaz, J. L.","Mangas, A.","Carbayo-Herencia, J. A.","Ruiz-Ocaña, P.","Lamíquiz-Moneo, I.","Mosquera, D.","Sáenz, P.","Masana, L.","Muñiz-Grijalvo, O.","Pérez-Calahorra, S.","Valdivielso, P.","Spanish Dyslipidemia Registry"],"year":2018,"bibtype":"article","biburl":"https://bibbase.org/zotero/Bibliotecacst","bibdata":{"bibtype":"article","type":"article","title":"Molecular basis of the familial chylomicronemia syndrome in patients from the National Dyslipidemia Registry of the Spanish Atherosclerosis Society","issn":"1933-2874","doi":"10.1016/j.jacl.2018.07.013","abstract":"BACKGROUND: Familial chylomicronemia syndrome (FCS) is an extremely rare lipoprotein disorder caused by mutations in at least 5 genes of the lipoprotein lipase (LPL) complex. OBJECTIVE: This work shows the molecular analysis of patients diagnosed with FCS, who attended the Spanish Arteriosclerosis Society lipid units and were included in the National Dyslipidemia Registry. METHODS: Among the 238 patients registered with severe hypertriglyceridemia (fasting triglycerides \\textgreater1000 mg/dL), 26 were diagnosed with FCS as they had confirmed postheparin plasma LPL activity deficiency and/or homozygosity for loss-of-function mutations in LPL, GPIHBP1, APOC2, LMF1, or Apolipoprotein A5 (APOA5). RESULTS: Among the 26 FCS cases, 23 had mutations in the homozygous state: 19 in LPL and 4 in the GPIHBP1 gene. The molecular analysis revealed 3 novel mutations: 2 in LPL, in 2 unrelated patients (c.312delA; p.Asp105Thrfs*66 and c.629A\\textgreaterG; p.His210Arg), and 1 in GPHIBP1 in a third patient (c.502delC; p.Leu168Serfs*83). These 3 patients had confirmed lack of LPL activity. Three additional patients with confirmed LPL activity deficiency were heterozygous carriers of mutations in the genes analyzed. Among these, we found 2 novel mutations in APOA5 (c.50-1G\\textgreaterA and c.326_327insC; p.Tyr110Leufs*158). CONCLUSION: We have identified 5 novel pathogenic mutations: 2 in LPL, 1 in GPIHBP1, and 2 in the APOA5 gene. The genetic defaults accounting for the LPL activity deficiency of 23 of them have been clearly identified and 3 patients, who harbored mutations in heterozygosity, were diagnosed based on LPL activity deficiency, which raises the question of the involvement of new genes in the manifestation of FCS.","language":"eng","journal":"Journal of Clinical Lipidology","author":[{"propositions":[],"lastnames":["Ariza"],"firstnames":["María","José"],"suffixes":[]},{"propositions":[],"lastnames":["Rioja"],"firstnames":["José"],"suffixes":[]},{"propositions":[],"lastnames":["Ibarretxe"],"firstnames":["Daiana"],"suffixes":[]},{"propositions":[],"lastnames":["Camacho"],"firstnames":["Ana"],"suffixes":[]},{"propositions":[],"lastnames":["Díaz-Díaz"],"firstnames":["José","Luis"],"suffixes":[]},{"propositions":[],"lastnames":["Mangas"],"firstnames":["Alipio"],"suffixes":[]},{"propositions":[],"lastnames":["Carbayo-Herencia"],"firstnames":["Julio","A."],"suffixes":[]},{"propositions":[],"lastnames":["Ruiz-Ocaña"],"firstnames":["Pablo"],"suffixes":[]},{"propositions":[],"lastnames":["Lamíquiz-Moneo"],"firstnames":["Itziar"],"suffixes":[]},{"propositions":[],"lastnames":["Mosquera"],"firstnames":["Daniel"],"suffixes":[]},{"propositions":[],"lastnames":["Sáenz"],"firstnames":["Pedro"],"suffixes":[]},{"propositions":[],"lastnames":["Masana"],"firstnames":["Luis"],"suffixes":[]},{"propositions":[],"lastnames":["Muñiz-Grijalvo"],"firstnames":["Ovidio"],"suffixes":[]},{"propositions":[],"lastnames":["Pérez-Calahorra"],"firstnames":["Sofía"],"suffixes":[]},{"propositions":[],"lastnames":["Valdivielso"],"firstnames":["Pedro"],"suffixes":[]},{"firstnames":[],"propositions":[],"lastnames":["Spanish Dyslipidemia Registry"],"suffixes":[]}],"month":"August","year":"2018","pmid":"30150141","keywords":"Article, Candidate genes, Causative mutation, Familial chylomicronemia syndrome, LPL activity, LPL mass, Medicina Interna","bibtex":"@article{ariza_molecular_2018,\n\ttitle = {Molecular basis of the familial chylomicronemia syndrome in patients from the {National} {Dyslipidemia} {Registry} of the {Spanish} {Atherosclerosis} {Society}},\n\tissn = {1933-2874},\n\tdoi = {10.1016/j.jacl.2018.07.013},\n\tabstract = {BACKGROUND: Familial chylomicronemia syndrome (FCS) is an extremely rare lipoprotein disorder caused by mutations in at least 5 genes of the lipoprotein lipase (LPL) complex.\nOBJECTIVE: This work shows the molecular analysis of patients diagnosed with FCS, who attended the Spanish Arteriosclerosis Society lipid units and were included in the National Dyslipidemia Registry.\nMETHODS: Among the 238 patients registered with severe hypertriglyceridemia (fasting triglycerides {\\textgreater}1000 mg/dL), 26 were diagnosed with FCS as they had confirmed postheparin plasma LPL activity deficiency and/or homozygosity for loss-of-function mutations in LPL, GPIHBP1, APOC2, LMF1, or Apolipoprotein A5 (APOA5).\nRESULTS: Among the 26 FCS cases, 23 had mutations in the homozygous state: 19 in LPL and 4 in the GPIHBP1 gene. The molecular analysis revealed 3 novel mutations: 2 in LPL, in 2 unrelated patients (c.312delA; p.Asp105Thrfs*66 and c.629A{\\textgreater}G; p.His210Arg), and 1 in GPHIBP1 in a third patient (c.502delC; p.Leu168Serfs*83). These 3 patients had confirmed lack of LPL activity. Three additional patients with confirmed LPL activity deficiency were heterozygous carriers of mutations in the genes analyzed. Among these, we found 2 novel mutations in APOA5 (c.50-1G{\\textgreater}A and c.326\\_327insC; p.Tyr110Leufs*158).\nCONCLUSION: We have identified 5 novel pathogenic mutations: 2 in LPL, 1 in GPIHBP1, and 2 in the APOA5 gene. The genetic defaults accounting for the LPL activity deficiency of 23 of them have been clearly identified and 3 patients, who harbored mutations in heterozygosity, were diagnosed based on LPL activity deficiency, which raises the question of the involvement of new genes in the manifestation of FCS.},\n\tlanguage = {eng},\n\tjournal = {Journal of Clinical Lipidology},\n\tauthor = {Ariza, María José and Rioja, José and Ibarretxe, Daiana and Camacho, Ana and Díaz-Díaz, José Luis and Mangas, Alipio and Carbayo-Herencia, Julio A. and Ruiz-Ocaña, Pablo and Lamíquiz-Moneo, Itziar and Mosquera, Daniel and Sáenz, Pedro and Masana, Luis and Muñiz-Grijalvo, Ovidio and Pérez-Calahorra, Sofía and Valdivielso, Pedro and {Spanish Dyslipidemia Registry}},\n\tmonth = aug,\n\tyear = {2018},\n\tpmid = {30150141},\n\tkeywords = {Article, Candidate genes, Causative mutation, Familial chylomicronemia syndrome, LPL activity, LPL mass, Medicina Interna},\n}\n\n","author_short":["Ariza, M. 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