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
ISSN: 19332874
Editorial
ELSEVIER SCIENCE INC, STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 12 Número: 6
Páginas: 1452-1462
WOS Id: 000454674600015
ID de PubMed: 30293936
imagen Open Access

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