Expanded newborn screening for inborn errors of metabolism (IEMs) by tandem mass spectrometry (MS/MS) could simultaneously analyze more than 40 metabolites and identify about 50 kinds of IEMs. Next generation sequencing (NGS) targeting hundreds of IMEs-associated genes as a follow-up test in expanded newborn screening has been used for genetic analysis of patients. The spectrum, prevalence, and genetic characteristic of IEMs vary dramatically in different populations. To determine the spectrum, prevalence, and gene mutations of IEMs in newborns in Suzhou, China, 401,660 newborns were screened by MS/MS and 138 patients were referred to genetic analysis by NGS. The spectrum of 22 IEMs were observed in Suzhou population of newborns, and the overall incidence (excluding short chain acyl-CoA dehydrogenase deficiency (SCADD) and 3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD)) was 1/3,163. The prevalence of each IEM ranged from 1/401,660 to 1/19,128, while phenylketonuria (PKU) (1/19,128) and Mild hyperphenylalaninemia (M-HPA) (1/19,128) were the most common IEMs, followed by primary carnitine uptake defect (PCUD) (1/26,777), SCADD (1/28,690), hypermethioninemia (H-MET) (1/30,893), 3-MCCD (1/33,412) and methylmalonic acidemia (MMA) (1/40,166). Moreover, 89 reported mutations and 51 novel mutations in 25 IMEs-associated genes were detected in 138 patients with one of 22 IEMs. Some hotspot mutations were observed for ten IEMs, including PAH gene c.728G > A, c.611A > G, and c.721C > T for Phenylketonuria, PAH gene c.158G > A, c.1238G > C, c.728G > A, and c.1315+6T > A for M-HPA, SLC22A5 gene c.1400C > G, c.51C > G, and c.760C > T for PCUD, ACADS gene c.1031A > G, c.164C > T, and c.1130C > T for SCAD deficiency, MAT1A gene c.791G > A for H-MET, MCCC1 gene c.639+2T > A and c.863A > G for 3-MCCD, MMUT gene c.1663G > A for MMA, SLC25A13 gene c.IVS16ins3Kb and c.852_855delTATG for cittrullinemia II, PTS gene c.259C > T and c.166G > A for Tetrahydrobiopterin deficiency, and ACAD8 gene c.1000C > T and c.286C > A for Isobutyryl coa dehydrogenase deficiency. All these hotspot mutations were reported to be pathogenic or likely pathogenic, except a novel mutation of ACAD8 gene c.286C > A. These mutational hotspots could be potential candidates for gene screening and these novel mutations expanded the mutational spectrum of IEMs. Therefore, our findings could be of value for genetic counseling and genetic diagnosis of IEMs.

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This study explored the effectiveness of expanding newborn screening (NBS) by tandem mass spectrometry (TMS) and gene diagnosis by next-generation sequencing (NGS). First, we described the characteristics of gene variants in Jiangsu Province. We collected clinical data from three NBS centers. All infants followed a unified screening and diagnosis process. After obtaining informed consent, dried blood spots (DBSs) were collected and analyzed by TMS. If the results fell outside of the cut-off value, repeat analysis was performed. If the re-test results remained abnormal, the infant was recalled for further assessment. We performed targeted sequencing using the extended edition panel of inborn errors of metabolism (IEM) to detect 306 genes using the Illumina HiSeq 2500 platform. A total of 536,008 babies underwent NBS by TMS in three NBS centres. In total, 194 cases were eventually diagnosed with various types of inherited metabolic diseases, with an overall incidence of 1/2763. There were 23 types of diseases, including ten amino acid disorders (43.5%), eight organic acidaemias (34.8%) and five fatty acid oxidation defects (21.7%). In these infants, we clearly identified variants of disease-causing genes by next-generation sequencing (NGS). Most had two variants and others had one or three variants: 88% of gene variants were heterozygous and 12% were homozygous. There is a certain incidence of IEM in Jiangsu Province and it is necessary to carry out screening for 27 diseases. Meanwhile, NGS combined with TMS offers an enhanced plan for NBS for IEM.

The CT genotype of NFE2L2-ins1 + C11108T and the TT genotype of GST01-C428T are susceptible factors for CHD. The AG, GG and (AG + GG) genotypes of DHFR-c594 + 59del19 are protective genotypes for CHD. Compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G) may increase the risk of CHD.

A simple, economic, and effective mechanical vibration method was introduced into the solidification process of A356 aluminum alloy during the expendable pattern shell casting process, and the effects of vibration frequency on microstructure, mechanical properties, and fracture behavior of the A356 alloy were investigated. Obtained results showed that the sizes and morphologies of α-Al primary phase and eutectic silicon particles were significantly improved by the mechanical vibration, and the mechanical properties and density of the A356 alloy greatly increased. With increasing vibration frequency, the grain size and secondary dendrite arm spacing (SDAS) continuously decreased, and the shape factor increased, and the mechanical properties and density of the A356 alloy gradually increased. With a vibration frequency of 100 Hz, the grain size and SDAS decreased by 32 and 19 %, respectively, and the shape factor increased by 262 %, and the average length, width, and aspect ratio of the silicon particles decreased by 45, 6, and 42 %, respectively, compared to that of the sample without vibration. Meanwhile, the tensile strength, yield strength, elongation, and hardness of the A356 alloy sample were, respectively, 35, 42, 57, and 28 % higher than those of the sample without vibration. In addition, the mechanical vibration changed the fractograph of the A356 alloy from a clear brittle fracture nature of the alloy without vibration to an obvious dimple fracture nature, and with the increase of vibration frequency, the dimples were very deep and well distributed with a high density.

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The cSMART assay applied to cell-free DNA isolated from maternal plasma of pregnant women is highly accurate for calling correct fetal NSHL genotypes. © 2016 John Wiley & Sons, Ltd.

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