2026-04-13T08:16:00Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4654512026-03-28T08:14:47Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Martín-Campos, Jesús María author Plana, Núria author Figueras, Rosaura author Ibarretxe, Daiana author Caixàs i Pedragós, Assumpta author Esteve, Eduardo author Pérez Pérez, Antonio author Bueno, Marta author Mauri Pont, Marta author Roig, Rosa author Martínez Figueroa, Susana author Pintó, Xavier author Masana, Luis author Julve i Gil, Josep author Blanco Vaca, Francisco author 2018 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. Cardiovascular risk Dutch Lipid Clinic Network score Familial hypercholesterolemia Molecular diagnosis Polygenic hypercholesterolemia Autosomal dominant hypercholesterolemia in Catalonia : Correspondence between clinical-biochemical and genetic diagnostics in 967 patients studied in a multicenter clinical setting