Dohndonaldson4424

To identify genetic variants among patients with methylmalonic acidemia and provide genetic evidence for prenatal diagnosis.

Thirty-one probands and their parents were subjected to next generation sequencing (NGS). Suspected variants were verified by Sanger sequencing.

25 probands or their parents were found to harbor previously known pathogenic or likely pathogenic variants, and three probands were found to carry heterozygous MMACHC exonic deletion. The overall diagnostic yield was 90.32%.

NGS can improve the detection rate for methylmalonic acidemia for its accuracy and efficiency, yet the detection of exonic deletion is required to further improve the diagnostic yield. The identification of specific variants provided evidence for prenatal diagnosis.

NGS can improve the detection rate for methylmalonic acidemia for its accuracy and efficiency, yet the detection of exonic deletion is required to further improve the diagnostic yield. The identification of specific variants provided evidence for prenatal diagnosis.

To investigate the clinical features of fetuses with Wolf-Hirschhorn syndrome(WHS) and explore the diagnostic methods and prenatal ultrasound characteristics and provide evidence for prenatal genetic counseling.

We retrospectively analyzed 5 cases of WHS fetuses diagnosed from March 2016 to February 2020, and analyzed the results of chromosomal karyotype analysis and chromosomal microarray analysis (CMA) of the fetuses.

Five cases of WHS were detected by CMA, four cases were detected by karyotype analysis. Prenatal ultrasound revealed 4 abnormalities, of which 3 had intrauterine growth restriction, and only 1 had abnormalities of the maxillofacial region. The sequence of the fragments was 4p16.3p16.1 with a loss of 6.5 Mb, 4p16.3p15.32 with a loss of 15.6 Mb combined with 2p25.3 increased by 906kb, 4p16.3p15.31 with a loss of 20.4 Mb, 4p16.p15.1 with a loss of 35 Mb and 4p16.3p14 with a loss of 37 Mb.

Fetal growth restriction may be one of the early manifestations of WHS. Absence of fetal facial abnormality by prenatal ultrasound screening cannot exclude WHS. Karyotype analysis may miss the diagnosis of WHS, while combined CMA techniques can improve the diagnostic accuracy.

Fetal growth restriction may be one of the early manifestations of WHS. Absence of fetal facial abnormality by prenatal ultrasound screening cannot exclude WHS. Karyotype analysis may miss the diagnosis of WHS, while combined CMA techniques can improve the diagnostic accuracy.

To identify the pathogenesis in two patients of restrictive cardiomyopathy (RCM) using high-throughput sequencing.

Peripheral blood samples from the two patients and their parents were collected and genomic DNAs were extracted to conduct targeted next generation sequencing or whole exome sequencing. Bioinformation analysis was performed to identify the pathogenic variants in genes associated with cardiomyopathy, which were further validated by Sanger sequencing.

By high throughput sequencing, we detected a de novo heterozygous variant c.549+1G>T in TNNI3 gene in patient 1. The variant has not been reported previously and was predicted to be pathogenic in line with American College of Medical Genetics and Genomics (ACMG) guidelines (PVS1+PS2+PM2). Another heterozygous variant c.433C>T (p.Arg145Trp) in TNNI3 gene was identified in patient 2 and his father. The variant had been reported as pathogenic variant in Clinvar and HGMD databases; based on ACMG guidelines, the variant was predicted to be likely pathogenic (PS3+PM1+PP3).

TNNI3 variants may be the causative gene responsible for restrictive cardiomyopathy in the two patients. High throughput sequencing results provide bases for the diagnosis of restrictive cardiomyopathy.

TNNI3 variants may be the causative gene responsible for restrictive cardiomyopathy in the two patients. High throughput sequencing results provide bases for the diagnosis of restrictive cardiomyopathy.

To identify the pathogenic variants of 4 patients with hemolytic anemia of unknown cause.

Peripheral blood samples of the patients and their family members were collected to extract DNA. The coding region and splice region in all exons of gene of erythrocyte related diseases were analyzed by using target sequence capture and high-throughput sequencing technology. Suspected pathogenic variants were verified by PCR combined Sanger sequencing technology.

Each of the probands was detected two compound heterozygous variants, and CDA II was diagnosed. Six variants were detected in the 4 probands, four variants were reported and the other two were first reported.

By high-throughput sequencing, gene variant of CDA II be analyzed fast and accurately. It is an effective supplement to convenional diagnostic methods. Furthermore, the novel variant sites have enriched the variant database of the SEC23B gene.

By high-throughput sequencing, gene variant of CDA II be analyzed fast and accurately. It is an effective supplement to convenional diagnostic methods. Furthermore, the novel variant sites have enriched the variant database of the SEC23B gene.

To explore the genetic etiology for a Chinese pedigree affected with Angelman syndrome (AS).

The proband with phenotypes suggestive of AS was subjected to copy number variation sequencing (CNV-seq), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and high-throughput next generation sequencing (NGS). Variant of the UBE3A gene was verified among family members by Sanger sequencing and bioinformatic analysis.

NGS revealed that the proband has carried a heterozygous variant of the UBE3A gene, namely c.1517G>A (p.R506H). The variant has co-segregated with the disease in the pedigree. Multiple amino acid sequence alignment showed that the site of mutant residue is conserved among nine homologous species. The variant was predicted to be deleterious by bioinformatic analysis.

A novel variant of the UBE3A gene has been identified in a Chinese pedigree affected with AS. Above finding has further expanded the spectrum of UBE3A gene variants and phenotypes of AS, which also facilitated molecular diagnosis and genetic counseling for the family.

A novel variant of the UBE3A gene has been identified in a Chinese pedigree affected with AS. Above finding has further expanded the spectrum of UBE3A gene variants and phenotypes of AS, which also facilitated molecular diagnosis and genetic counseling for the family.

To analyze a pathogenic variant of MEFV gene in a family with autosomal dominant-familial Mediterranean fever (AD-FMF).

A 5-year-old boy presented with recurrent aseptic meningitis and his major symptoms included recurrent fever with headache and vomiting. His family members including his mother, sister and brother also had recurrent fever. A genetic disease was considered. DNAs were extracted from patient and all his family members' blood samples. Whole exome sequencing was performed to identify putative pathogenic variants that can explain this family's condition and Sanger sequencing was conducted. The impact of detected variants were predicted and validated by bioinformatics.

A missense variant c.2229C>G (p.Phe743Leu) in MEFV gene was identified in the proband and his family members including his mother, sister and brother. This variant had not been reported in China previously, but the locus of it had already been reported in Arabic patient with AD-FMF (PS1). This variant was absent in major allfor the further understanding of AD-FMF.

G (p.Phe743Leu) in MEFV gene. The recurrent aseptic meningitis was a very rare manifestation in AD-FMF patients and had not been reported in China previously. The clinical and genetic findings of the present study are helpful for the further understanding of AD-FMF.

The sleep clinical record (SCR) has been used to diagnose obstructive sleep apnea syndrome (OSAS) in children when access to polysomnography (PSG) is limited. Our aim was to determine the best SCR score that could facilitate diagnosis of moderate-to-severe OSAS in children with snoring.

Healthy children with history of snoring, who were referred for PSG, were prospectively recruited. The SCR score was calculated. Receiver operating characteristic curves (ROCs) were plotted to determine the area under curve (AUC), and the optimum SCR cutoff value was determined using the Youden index (J).

Two hundred and seventy-three children were recruited (mean age 6.3 ± 2.5years; median obstructive apnea-hypopnea index 1.5 episodes/h; range 0-61.1). The mean SCR score was 6.9 ± 3.6. Forty-six children had moderate-to-severe OSAS. Subjects with moderate-to-severe OSAS had a significantly higher mean SCR score (10.2 ± 2.9) than those with mild OSAS (6.2 ± 3.3; P < 0.001). Based on the plotted ROC, the AUC was 0.811 (95% confidence interval 0.747-0.876; P < 0.001). Calculation of J, based on its ROC coordinates, indicated that the optimum cutoff SCR score to predict moderate-to-severe OSAS was 8.25, corresponding to a sensitivity of 83% and a specificity of 70%.

Among children with history of snoring, an SCR score above 8.25 can identify those with moderate-to-severe OSAS.

Among children with history of snoring, an SCR score above 8.25 can identify those with moderate-to-severe OSAS.Contezolid (Youxitai ®), an orally administered oxazolidinone antibacterial agent, is being developed by Shanghai MicuRx Pharmaceutical Co., Ltd. for the treatment of multidrug-resistant (MDR) Gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. In June 2021, it was approved by the National Medical Products Administration of China for the treatment of complicated skin and soft tissue infections (cSSTI), including, but not limited to, methicillin-susceptible S. https://www.selleckchem.com/products/abt-199.html aureus, MRSA, Streptococcus pyogenes and Streptococcus agalactiae. The recommended dosage of contezolid is 800 mg (i.e. two 400 mg tablets) every 12 h for 7-14 days. Contezolid is also undergoing clinical development for acute bacterial skin and skin structure infections (ABSSSI) in the USA, and for diabetic foot infections. This article summarizes the milestones in the development of contezolid leading to this first approval for the treatment of cSSTI.Ecosystem water use efficiency (eWUE), defined as the ratio between carbon gains and water loss from the system, has been recognized as an important characteristic of carbon and water balances. The long-lasting "Grain for Green" Program (GFGP) initiated in 1999 in China's Loess Plateau (CLP) is a large-scale ecological program in the world, which aims to improve the CLP's ecosystem resilience by enhancing vegetation cover and productivity. Understanding how the GFGP can affect eWUE is imperative to ensuring sustainable water resources and to promoting sustainable management strategies. In this study, we evaluated the spatiotemporal variability of growing-season eWUE and examined its response to both climate change and vegetation coverage from 1982 to 2017. Our results indicate that growing-season eWUE, gross primary productivity (GPP), and evapotranspiration (ET) in CLP area increased significantly from 1982 to 2017. Specifically, eWUE, GPP, and ET increased more rapidly after China established the program. The most significant growth area of eWUE was found in main areas conducting GFGP project, including the Loess hilly and gully area (LHGA).