Autosomal dominant hypercholesterolemia in Catalonia : Correspondence between clinical-biochemical and genetic diagnostics in 967 patients studied in a multicenter clinical setting
Martín-Campos, Jesús M. (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Plana, Núria (Hospital Universitari Sant Joan de Reus (Tarragona))
Figueras, Rosaura (Hospital Universitari de Bellvitge)
Ibarretxe, Daiana (Hospital Universitari Sant Joan de Reus (Tarragona))
Caixàs i Pedragós, Assumpta (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Esteve, Eduardo (Hospital Universitari de Girona Doctor Josep Trueta)
Pérez Pérez, Antonio (Institut d'Investigació Biomèdica Sant Pau)
Bueno, Marta (Hospital Arnau de Vilanova (Lleida, Catalunya))
Mauri, Marta (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Roig, Rosa (Institut d'Investigació Biomèdica Sant Pau)
Martínez Figueroa, Susana (Institut d'Investigació Biomèdica Sant Pau)
Pintó, Xavier (Hospital Universitari de Bellvitge)
Masana, Luis (Hospital Universitari Sant Joan de Reus (Tarragona))
Julve i Gil, Josep (Institut d'Investigació Biomèdica Sant Pau)
Blanco Vaca, Francisco (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2018
Resum:	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 probands. 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.
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Estudi clínic ; recerca ; Versió acceptada per publicar
Matèria:	Cardiovascular risk ; Dutch Lipid Clinic Network score ; Familial hypercholesterolemia ; Molecular diagnosis ; Polygenic hypercholesterolemia
Publicat a:	Journal of Clinical Lipidology, Vol. 12 N. 6 (Nov. 2018) , p. 1452-1462, ISSN 1876-4789

DOI: 10.1016/j.jacl.2018.09.002
PMID: 30293936

36 p, 291.8 KB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d’Investigació i Innovació Parc Taulí (I3PT)
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