崔凯
中国医学科学院阜外医院 实验诊断中心
AIM:Familial hypercholesterolemia (FH) is the most commonly encountered genetic condition that predisposes individuals to severe autosomal dominant lipid metabolism dysfunction. Although more than 75% of the European population has been scrutinized for FH-causing mutations, the genetic diagnosis proportion among Chinese people remains very low (less than 0.5%). The aim of this study was to identify genetic mutations and help make a precise diagnosis in Chinese FH patients.METHODS:We designed a gene panel containing 20 genes responsible for FH and tested 208 unrelated Chinese possible/probable or definite FH probands. In addition, we called LDLR copy number variation (CNVs) with the panel data by panelcn.MOPS, and multiple ligation-dependent probe amplification (MLPA) was used to search for CNVs in LDLR, APOB, and PCSK9.RESULTS:A total of 79 probands (38.0%) tested positive for a (likely) pathogenic mutation, most of which were LDLR mutations, and three LDLR CNVs called from the panel data were all successfully confirmed by MLPA analysis. In total, 48 different mutations were identified, including 45 LDLR mutations, 1 APOB mutation, 1 ABCG5 mutation, and 1 APOE mutation. Among them, the five most frequent mutations (LDLR c.1879G＞A, c.1747C＞T, c.313＋1G＞A, c.400T＞C, and APOB c.10579C＞T) were detected. Moreover, we also found that patients with LDLR variants of CNVs and splicing and nonsense had increased low-density lipoprotein cholesterol levels when compared with those who carried missense variants.CONCLUSIONS:The spectrum of FH-causing mutations in the Chinese population is refined and expanded. Analyses of FH causal genes have been a great help in clinical diagnosis and have deep implications in disease treatment. These data can serve as a considerable dataset for next-generation sequencing analysis of the Chinese population with FH and contribute to the genetic diagnosis and counseling of FH patients.
Journal of atherosclerosis and thrombosis 2020
BACKGROUND:Point-of-care (POC) cTn assays are needed when the central laboratory is unable to provide timely results to the emergency department. Many POC devices are available. The prospect of choosing them is daunting. In order to provide a quick decision-making reference for POC cTn device selection comparing them to the central laboratory, seven POC devices commonly employed by emergency department were evaluated.METHODS:Firstly, we reviewed all devices package inserts. Secondly, we evaluated several POC cTn assays for imprecision, linearity, and correlation with central laboratory assays according to CLSI EP protocols. The linear regression analyses were performed only for the detectable concentrations. Five cTnI devices (Alere Triage, BioMerieux Vidas, Mitsubishi Pathfast, ReLIA TZ-301, and Radiometer AQT90) were evaluated against a contemporary cTnI assay (Beckman Access II Accu TnI). Two cTnT assays (Radiometer AQT90 and Roche Cobas h232) were compared to a high-sensitivity (hs) cTnT method (Roche Cobas e601).RESULTS:For cTn levels around the 99th percentile upper reference limits (URLs) of the comparator assays, imprecision could not be assessed for the Alere, BioMerieux, and Cobas h232 as they gave undetectable readings due to a lack of assay sensitivity. Imprecision (CV) was unacceptably high for the ReLIA (33.3%). On account of this precision metric, these four assays were deemed unsuitable. Regression analyses showed acceptable linearity for all the POC devices. The correlation coefficients for ReLIA, BioMerieux, Cobas h232, and Radiometer cTnT were >0.95. Unlike the cTnT devices, the cTnI assays employ different capture and detection antibodies leading to non-commutable results. The POC cTn results were concordant with their comparator-Radiometer cTnT 90%, Pathfast cTnI 85%, and Radiometer cTnI 75%.CONCLUSION:Our study provides the procedure and essential data to guide selection of a POC cTn device. Of the point-of-care devices, methods evaluated Radiometer AQT90 (cTnI and cTnT) and Pathfast might be considered.
Journal of clinical laboratory analysis 2020
