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Pathogenic variants in the argininosuccinate lyase (ASL) gene have been shown to cause argininosuccinate lyase deficiency (ASLD); therefore, sequencing analysis offers advantages for prenatal testing and counseling in families afflicted with this condition. Here, we performed a genetic analysis of an ASLD patient and his family with an aim to offer available information for clinical diagnosis. The research subjects were a 23-month-old patient with a high plasma level of citrulline and his unaffected parents. Whole-exome sequencing identified potential related ASL gene mutations in this trio. Enzymatic activity was detected spectrophotometrically by a coupled assay using arginase and measuring urea production. We identified a novel nonsynonymous mutation (c.206A>G, p.Lys69Arg) and a stop mutation (c.637C>T, p.Arg213∗) in ASL in a Chinese Han patient with ASLD. The enzymatic activity of a p.Lys69Arg ASL construct in human embryonic kidney 293T cells was significantly reduced compared to that of the wild-type construct, and no significant activity was observed for the p.Arg213∗ construct. Compound heterozygous p.Lys69Arg and p.Arg213∗ mutations that resulted in reduced ASL enzyme activity were found in a patient with ASLD. This finding expands the clinical spectrum of ASL pathogenic variants. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate ITGA2B and ITGB3 genetic polymorphisms and to evaluate the variability in the platelet function in healthy Chinese subjects. The genetic sequence of the entire coding region of the ITGA2B and ITGB3 genes was investigated. Adenosine diphosphate-induced platelet aggregation, glycoprotein IIb/IIIa content, bleeding time, and coagulation indexes were detected. Thirteen variants in the ITGA2B locus and 29 variants in the ITGB3 locus were identified in the Chinese population. The rs1009312 and rs2015049 were associated with the mean platelet volume. The rs70940817 was significantly correlated with the prothrombin time. The rs70940817 and rs112188890 were related with the activated partial thromboplastin time, and ITGB3 rs4642 was correlated with the thrombin time and fibrinogen. The minor alleles of rs56197296 and rs5919 were associated with decreased ADP-induced platelet aggregation, and rs55827077 was related with decreased GPIIb/IIIa per platelet. The rs1009312, rs2015049, rs3760364, rs567581451, rs7208170, and rs117052258 were related with bleeding time. Further studies are needed to explore the clinical importance of ITGA2B and ITGB3 SNPs in the platelet function. [ABSTRACT FROM AUTHOR]