Autosomal dominant hypercholesterolemia in Catalonia: Correspondence between clinical-biochemical and genetic diagnostics in 967 patients studied in a multicenter clinical setting
Por:
Martin-Campos, JM, Plana, N, Figueras, R, Ibarretxe, D, Caixas, A, Esteve, E, Perez, A, Bueno, M, Mauri, M, Roig, R, Martinez, S, Pinto, X, Masana, L, Julve, J, Blanco-Vaca, F, Argimon, J, Arroyo, JA, Matas, L, Carreras, G, Anglada, J, Perea, V, Borrallo, RM, Garcia, M, Grau, J, Guerrero, C, Montaner, P, Guiterrez, L, Llargues, E, Vila, M, Sanchez, E, Morales, C, Mujal, A, Sola, J, Cano, A, Ros, E, Zambon, D, Ramirez, R, Soler, C, Vila, A, Zamora, A, Vila, L, Jerico, C
Publicada:
1 dic 2018
Resumen:
BACKGROUND: Autosomal dominant hypercholesterolemia (ADH) is associated with mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes, and it is estimated to be greatly underdiagnosed. The most cost-effective strategy for increasing ADH diagnosis is a cascade screening from mutation-positive pro bands.
OBJECTIVE: The objective of this study was to evaluate the results from 2008 to 2016 of ADH genetic analysis performed in our clinical laboratory, serving most lipid units of Catalonia, a Spanish region with approximately 7.5 million inhabitants.
METHODS: After the application of the Dutch Lipid Clinic Network (DLCN) clinical diagnostic score for ADH, this information and blood or saliva from 23 different lipid clinic units were investigated in our laboratory. DNA was screened for mutations in LDLR, APOB, and PCSK9, using the DNA-array LIPOchip, the next-generation sequencing SEQPRO LIPO RS platform, and multiplex ligation dependent probe amplification (MLPA). The Simon Broome Register Group (SBRG) criteria was calculated and analyzed for comparative purposes.
RESULTS: A total of 967 unrelated samples were analyzed. From this, 158 pathogenic variants were detected in 356 patients. The main components of the DLCN criteria associated with the presence of mutation were plasma LDL cholesterol (LDLc), age, and the presence of tendinous xanthomata. The contribution of family history to the diagnosis was lower than in other studies. DLCN and SBRG were similarly useful for predicting the presence of mutation.
CONCLUSION: In a real clinical practice, multicenter setting in Catalonia, the percentage of positive genetic diagnosis in patients potentially affected by ADH was 38.6%. The DLCN showed a relatively low capacity to predict mutation detection but a higher one for ruling out mutation. (C) 2018 National Lipid Association. All rights reserved.
Filiaciones:
Martin-Campos, JM:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Plana, N:
Univ Rovira & Virgili, Hosp Univ St Joan, Unitat Med Vasc & Metab,IISPV, Unitat Recerca Lipids & Arteriosclerosi,CIBERDEM, Reus, Spain
Figueras, R:
Univ Barcelona, Hosp Univ Bellvitge, Serv Med Interna, Unitat Lipids & Risc Vasc,IDIBELL,CIBEROBN,FIPEC, ABS 17 Setembre, Lhospitalet El Prat Llob, Spain
Ibarretxe, D:
Univ Rovira & Virgili, Hosp Univ St Joan, Unitat Med Vasc & Metab,IISPV, Unitat Recerca Lipids & Arteriosclerosi,CIBERDEM, Reus, Spain
Caixas, A:
Univ Autonoma Barcelona, Inst Invest & Innovacio Parc Tauli I3PT, Hosp Univ Parc Tauli, Serv Endocrinol Nutr, Sabadell, Spain
Esteve, E:
Hosp Univ Girona Dr Josep Trueta, Serv Endocrinol Nutr, CIBEROBN, Girona, Spain
Perez, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Bueno, M:
Hosp Arnau Vilanova, Serv Endocrinol & Nutr, Lleida, Spain
Mauri, M:
Hosp Terrassa, Serv Med Interna, Terrassa, Spain
Roig, R:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Martinez, S:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Pinto, X:
Univ Barcelona, Hosp Univ Bellvitge, Serv Med Interna, Unitat Lipids & Risc Vasc,IDIBELL,CIBEROBN,FIPEC, ABS 17 Setembre, Lhospitalet El Prat Llob, Spain
Masana, L:
Univ Rovira & Virgili, Hosp Univ St Joan, Unitat Med Vasc & Metab,IISPV, Unitat Recerca Lipids & Arteriosclerosi,CIBERDEM, Reus, Spain
Julve, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Blanco-Vaca, F:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Bioquim,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Endocrinol,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Bioquim & Biol Mol, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Med, Serv Nutr,IIB St Pau,CIBERDEM,Inst Recerca, Barcelona, Spain
Argimon, J:
Hosp Sagrat Cor, Barcelona, Spain
Arroyo, JA:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Matas, L:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Carreras, G:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Anglada, J:
Hosp Univ Mutua Terrassa, Terrassa, Spain
Perea, V:
Hosp Univ Mutua Terrassa, Terrassa, Spain
Borrallo, RM:
Hosp Terrassa, Terrassa, Spain
Garcia, M:
Hosp Gen Cataluna, Sant Cugat Del Valles, Spain
Grau, J:
Hosp Municipal Badalona, Badalona, Spain
Guerrero, C:
Hosp St Joan de Deu Martorell, Martorell, Spain
Montaner, P:
Hosp St Joan de Deu Martorell, Martorell, Spain
Guiterrez, L:
Hosp Arnau Vilanova, Lleida, Spain
Llargues, E:
Hosp Gen Granollers, Granollers, Spain
Vila, M:
Hosp Gen Granollers, Granollers, Spain
Sanchez, E:
Hosp Gen Granollers, Granollers, Spain
Morales, C:
Hosp St Joan de Deu Fundacio, Manresa, Spain
Mujal, A:
Hosp Univ Parc Tau1i, Sabadell, Spain
Sola, J:
Hosp Univ Parc Tau1i, Sabadell, Spain
Cano, A:
Hosp Univ Parc Tau1i, Sabadell, Spain
Ros, E:
Hosp Clin Barcelona, Barcelona, Spain
Zambon, D:
Hosp Clin Barcelona, Barcelona, Spain
Ramirez, R:
Hosp St Pau & Santa Tecla, Tarragona, Spain
Soler, C:
Hosp Santa Caterina, Salt, Spain
Vila, A:
Hosp Figueres, Figueres, Spain
Zamora, A:
Hosp Blanes, Blanes, Spain
Vila, L:
Hosp St Joan Despi Moises Broggi, St Joan Despi, Spain
Jerico, C:
Hosp St Joan Despi Moises Broggi, St Joan Despi, Spain
Open Access
|