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1.
J Vis Exp ; (150)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31475974

RESUMO

The discovery and development of immuno-oncology (I-O) therapy in recent years represents a milestone in the treatment of cancer. However, treatment challenges persist. Robust and disease-relevant animal models are vital resources for continued preclinical research and development in order to address a range of additional immune checkpoints. Here, we describe a human peripheral blood mononuclear cell (PBMC) - based humanized xenograft model. BGB-A317 (Tislelizumab), an investigational humanized anti-PD-1 antibody in late-stage clinical development, is used as an example to discuss platform set-up, model characterization and drug efficacy evaluations. These humanized mice support the growth of most human tumors tested, thus allowing the assessment of I-O therapies in the context of both human immunity and human cancers. Once established, our model is comparatively time- and cost-effective, and usually yield highly reproducible results. We suggest that the protocol outlined in this article could serve as a general guideline for establishing mouse models reconstituted with human PBMC and tumors for I-O research.

2.
Nano Lett ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487192

RESUMO

Amplitude, duration, and frequency of activation of the extracellular-signal-regulated kinase (ERK) pathway code distinct information to instruct cells to migrate, proliferate, or differentiate. Synchronized frequency control of ERK activation would provide a powerful approach to regulate cell behaviors. Here we demonstrated modulation of ERK activities using alternative current (AC) electric fields (EFs) applied through high-k dielectric passivated microelectrodes. Both the amplitude and frequency of ERK activation can be precisely synchronized and modulated. ERK activation in our system is independent of Faradaic currents and electroporation, thus excluding mechanisms of changes in pH, reactive oxygen species and other electro-chemical reaction. Further experiments pinpointed a mechanism of phosphorylation site of epidermal growth factor (EGF) receptor to activate the EGFR-ERK pathway, and independent of EGF. AC EFs thus provide a powerful platform for practical and precise control of EGFR-ERK pathway.

3.
J Hazard Mater ; 381: 120994, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31425912

RESUMO

The development of photocatalysts making full use of natural light sources is highly desired for the remediation of marine oil spill pollution, which is full of challenges. Herein, we demonstrate a well-defined visible-near-infrared-responsive g-C3N4Hx+ reduced decatungstate charge-transfer salt (RCD-CTS), which possess efficient light-absorption ability ranging from visible light to the near infrared region. The RCD-CTS photocatalyst exhibits excellent performance for photocatalytic removal of petroleum hydrocarbon. The structural characterization and theoretical calculation confirmed strong chemical interaction between components and partly reduction of decatungstate results in the plasmonic properties and the absorption of near infrared light. As a results, it is proposed that"hot electrons"transfer process generated by plasmon effect promotes the efficient separation of charge-carriers. Ultimately, this work sheds light on the discovery and application of visible-near-infrared-responsive optical materials that may be exploited further in artificial photosynthesis, solar energy conversion, and phototherapy.

4.
Ann Vasc Surg ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382001

RESUMO

INTRODUCTION: Multiple studies have demonstrated the benefits of creating arteriovenous fistulas (AVFs) under regional anesthesia. This is most likely due to the avoidance of hemodynamic instability and stress response of general anesthesia as well as the sympathectomy associated with brachial plexus blockade. Since vein diameter is the major limiting factor for primary AVFs creation and maturation, our aim is to investigate if the vasodilation that accompanies regional anesthesia leads to improved patency and maturation rate of autologous AVF and graft (AVG) patency compared to those placed under general anesthesia. METHODS: This retrospective study was approved by the Institutional Review Board. 238 patients that had either an AVF or an arteriovenous graft placed at Mayo Clinic Florida between 2012 and 2017 were analyzed. Demographics, access type, preoperative vein diameter, anesthesia type, change of plan after regional vs general anesthesia, and outcomes were assessed. All statistical tests were two-sided with the alpha level set at 0.05 for statistical significance. RESULTS: Among 238 patients, 120 (50.4%) patients underwent regional anesthesia. Difference between the two groups in risk factors, and 30-day or long-term outcomes (failure, abandonment, or reoperation) were not statistically significant. 58.5% of accesses placed under general anesthesia were abandoned compared to 45.2% of those placed under regional anesthesia. 25.8% of accesses placed under general anesthesia were abandoned due to loss of patency compared to 19.2% of those placed under regional anesthesia. Two-month failure was higher in the general anesthesia group compared to the regional anesthesia group (p=0.076). Following preoperative vein mapping, 22 patients were originally intended to have an arteriovenous graft placed under regional anesthesia. Following brachial plexus blockade, 9 of these patients (9/22: 41%) were successfully switched to AVF, while the other 13 followed the original surgical plan and received an AVG. Of these, 0 failed and 0 were abandoned due to loss of patency. CONCLUSIONS: This study showed possible improvement in failure rates for vascular accesses placed under regional anesthesia compared to those placed under general anesthesia. Additionally, we showed an impact of regional anesthesia on the surgical plan by transitioning from a planned AVG to an AVF, intraoperatively. Giving patients with originally inadequate vein diameter the chance to have the preferred hemodialysis access method by simply switching anesthesia type could reduce the number of grafts placed in favor of fistulas.

5.
J Vis Exp ; (149)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31403614

RESUMO

Information about toxicities of chemicals are essential in their application and waste management. For chemicals at low concentrations, the long-term effects are very important in judging their consequences in the environment and on human health. In demonstrating long-term influences, effects of chemicals over generations in recent studies provide new insight. Here, we describe protocols for studying effects of chemicals over multiple generations using free-living nematode Caenorhabditis elegans. Two aspects are presented: (1) trans-generational (TG) and (2) multi-generational effect studies, the latter of which is separated to multi-generational exposure (MGE) and multi-generational residual (MGR) effect studies. The TG effect study is robust with a simple purpose to determine whether chemical exposure to parents can result in any residual consequences on offspring. After the effects are measured on parents, sodium hypochlorite solutions are used to kill the parents and keep the offspring so as to facilitate effect measurement on the offspring. The TG effect study is used to determine whether the offspring are affected when their parent is exposed to the pollutants. The MGE and MGR effect study is systematical used to determine whether continuous generational exposure can result in adaptive responses in offspring over generations. Careful pick-up and transfer are used to distinguish generations to facilitate effect measurement on each generation. We also combined protocols to measure locomotion behavior, reproduction, lifespan, biochemical and gene expression changes. Some example experiments are also presented to illustrate the trans- and multi-generational effect studies.

6.
J Hazard Mater ; 382: 121061, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31470303

RESUMO

Increasing concerns are earned on the multigenerational hazards of antibiotics due to the connection between their mother-children transfer via cord blood and breast milk and obesity in the children. Currently, Caenorhabditis elegans was exposed to sulfamethoxazole (SMX) over 11 generations (F0-F10). Indicators of obesogenic effects and gene expressions were measured in each generation and also in T11 to T13 that were the offspring of F10. Biochemical analysis results showed that SMX stimulated fatty acids in most generations including T13. The stimulation was resulted from the balance between enzymes for fatty acid synthesis (e.g., fatty acid synthetase) and those for its consumption (e.g., fatty acid transport protein). Gene expression analysis demonstrated that the obesogenic effects of SMX involved peroxisome proliferator activated receptors (PPARs, e.g., nhr-49) and insulin/insulin-like signaling (IIS) pathways (e.g., ins-1, daf-2 and daf-16). Further epigenetic analysis demonstrated that SMX caused 3-fold more H3K4me3 binding genes than the control in F10 and T13. In F10, the most significantly activated genes were in metabolic and biosynthetic processes of various lipids, nervous system and development. The different gene expressions in T13 from those in F10 involved development, growth, reproduction and responses to chemicals in addition to metabolic processes.

7.
J Virol ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413136

RESUMO

Interferon (IFN) production activated by phosphorylated interferon regulatory factor 7 (IRF7) is a pivotal process during host antiviral infection. For viruses, suppressing the host IFN response is beneficial for viral proliferation; in such cases, evoking host-derived IFN negative regulators would be very useful for viruses. Here, we report that the zebrafish rapunzel 5 (RPZ5) protein which activated by virus degraded phosphorylated IRF7 is activated by TBK1, leading to the reduction of IFN production. Upon viral infection, zebrafish rpz5 was significantly upregulated as ifn, in response to the stimulation. Overexpression of RPZ5 blunted the IFN expression induced by both viral and retinoic acid-inducible gene I (RIG-I) like-receptor (RLR) factors. Subsequently, RPZ5 interacted with RLRs but did not affect the stabilization of the proteins in the normal state. Interestingly, RPZ5 degraded the phosphorylated IRF7 under TBK1 activation through K48-linked ubiquitination. Finally, overexpression of RPZ5 remarkably reduced the host cell antiviral capacity. These findings suggest that zebrafish RPZ5 is a negative regulator of phosphorylated IRF7 and attenuates IFN expression during viral infection, providing insight into the IFN balance mechanism in fish.IMPORTANCE The phosphorylation of IRF7 is helpful for host IFN production to defend against viral infection, thus, it is a potential target for viruses to mitigate the antiviral response. We report that the fish RPZ5 is an IFN negative regulator induced by fish viruses and degrades the phosphorylated IRF7 activated by TBK1, leading to IFN suppression and promoting viral proliferation. These findings reveal a novel mechanism for interactions between the host cell and viruses in the lower vertebrate.

9.
ChemSusChem ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444854

RESUMO

Transition metal selenides (TMSs) with significant electrochemical activity and high intrinsic electrical conductivity have lately attracted considerable attention due to their potential for energy storage devices. However, the low energy densities of the reported TMSs, originating from the small active surface area and poor electrolyte ion mobility, substantively restrict their application potential. In this work, porous ultrathin nickel selenide nanosheet networks (NiSe NNs) on nickel foam have been fabricated using a novel, facile method, i.e. selenylation/pickling the pre-formed manganese (Mn)-doped α-Ni(OH) 2 . Removal of Mn results in a highly porous structure to the NNs. The three-dimensional framework of the NNs and the inherent nature of NiSe afford high ion mobility, abundant accessible activated sites, vigorous electrochemical activity, and low resistance. Using the NNs as electrodes achieves one of the highest specific capacity of TMSs ever reported, i.e. 443 mA h g -1 (807 µAh cm -2 ) at 3.0 A g -1 . The assembled NiSe NNs//porous carbon hybrid supercapacitor delivers a high energy density of 66.6 Wh kg -1 at a power density of 425 W kg -1 , with excellent cycling stability. This work provides a new production strategy for novel electrode materials applied in high-performance hybrid supercapacitors, and a fresh path towards commercial applications of hybrid supercapacitors based on TMS electrodes.

10.
J Synchrotron Radiat ; 26(Pt 4): 1058-1068, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31274428

RESUMO

The optical design of a novel spectrometer is presented, combining a cylindrically convex pre-mirror with a cylindrically concave varied-line-spacing grating (both in the meridional) to deliver a resolving power of 100000-200000 in the `water window' (2-5 nm). Most remarkably, the extremely high spectral resolution is achieved for an effective meridional source size of 50 µm (r.m.s.); this property could potentially be applied to diagnose SASE-FEL and well resolve individual single spikes in its radiation spectrum. The overall optical aberrations of the system are well analysed and compensated, providing an excellent flat-field at the detector domain throughout the whole spectral range. Also, a machine-learning scheme - SVM - is introduced to explore and reconstruct the optimal system with high efficiency.

11.
Talanta ; 204: 344-352, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357303

RESUMO

Antibiotics are one of the emerging contaminants in water, which have a great impact on ecosystems and human health. It has been challenging to simultaneously realize low-cost, rapid, highly sensitive and selective detection of antibiotics with conventional methods. Here, we report luminescent chemosensors for detecting antibiotics in water, based on metal-organic framework (MOF), i.e., zeolitic imidazolate framework-8 (ZIF-8), loaded with rhodamine B (RhB) and fluorescein disodium salt (FSS) dyes. Compared with ZIF-8, the fluorescence signals of RhB@ZIF-8 and FSS@ZIF-8 were significantly improved and presented ultrahigh sensitivity to nitrofurans (NFAs) and tetracyclines (TCs) with fluorescence quenching and fluorescence enhancement in water, respectively. The unique structures and properties of RhB@ZIF-8 and FSS@ZIF-8 lead to outstanding sensitivities in antibiotic detection. For instance, the RhB@ZIF-8 sensor shows the lower limit of detection (LOD) of 0.26 µM to nitrofurantoin (NFT), 0.47 µM to nitrofurazone (NFZ), 0.11 µM to tetracycline (TC), and 0.14 µM to oxytetracycline (OTC); while the FSS@ZIF-8 sensor shows the LOD of 0.31 µM to NFT, 0.35 µM to NFZ, 0.17 µM to TC, and 0.16 µM to OTC. In addition, NFT and TC were also successfully detected by FSS@ZIF-8 in water from real water environment. The results indicate that dye@MOF-based luminescent composites are favorable for antibiotic detection, presenting great potentials in water quality monitoring.

12.
Water Res ; 163: 114883, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31362209

RESUMO

Phosphate, due to its somatotrophic effect on organisms, can cause severe eutrophication with excessive content in water. Conventional methods for phosphate detection, which are based on complicated instruments, are time-consuming. Here we report a luminescent lanthanide functionalized coordination polymer (Eu@BUC-14) by doping Eu3+ cations to BUC-14 nanocrystals. This Eu3+ functionalized hybrid (Eu@BUC-14) presents excellent luminescence features of Eu3+ ion that originated from efficient energy transfer from the ligand. The detection results show that Eu@BUC-14 is a highly efficient luminescent probe for phosphate detection in aqueous solutions, exhibiting high sensitivity with a low detection limit of 0.88 µM and a short response time of within 5 min. More significantly, Eu@BUC-14 has a high specificity for PO43- over fifteen other pollutant anions and eleven metal cations. The sensing mechanism is proposed via an in-depth analysis of the interaction between PO43- and Eu3+. Simultaneously, it displays high adsorption ability toward PO43- (57.9 mg P/g), making it an outstanding multifunctional material. And the adsorption process plays an important role in preconcentration of PO43- which can lead to a quick fluorescent response with high quenching efficiency. The practicality of Eu@BUC-14 was also validated by sensing PO43- in real environment water samples.

13.
Chemosphere ; 235: 858-866, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284134

RESUMO

Ammonia is a known environmental pollutant around the world. It leads to the deterioration of air quality and has adverse effects on human health. Although previous studies have demonstrated that ammonia caused some health problems to chickens, it is still unclear whether ammonia causes cardiac toxicity. The functional autophagy is very important for cardiac homeostasis. Therefore, the role of autophagy was investigated in the mechanism of chicken heart damage induced by environmental contaminant ammonia in our present study. The results from the oxidative stress index (SOD, GPx, H2O2, and MDA), NO content, iNOS activity, and transmission electron microscopy indicated that excess ammonia induced oxidative stress and autophagy in the chicken heart. The expression results from miR-202-5p and PTEN/AKT/mTOR (PTEN, LC3-I, LC3-II, p-AKT, AKT, Beclin1, Dynein, ATG5, p-mTOR and mTOR) signaling pathway-related genes further confirmed that excess ammonia induced cardiac autophagy. In conclusion, these results demonstrated that excess ammonia can cause cardiac damage and mediate mir-202-5p to regulate autophagy through PTEN/AKT/mTOR pathway in the chicken heart injury. Our findings will provide a new insight for better assessing the toxicity mechanism of environmental pollutants ammonia on the heart.

14.
Mol Ther Nucleic Acids ; 17: 198-209, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31261034

RESUMO

Given that the cDNA of F8 is too large to be packaged into adeno-associated virus (AAV) capsids, gene transfer of some versions of B-domain-deleted F8 (BDD-F8) for hemophilia A (HA) treatment has been attempted with promising results. Here, we describe an efficient gene correction via single-stranded-oligodeoxynucleotide (ssODN)-mediated in-frame deletion within the B domain of F8 with CRISPR/Cas9 in HA-patient-derived induced pluripotent stem cells (HA-iPSCs). The expression and activity of FVIII was restored in corrected HA-iPSC-derived induced endothelial progenitor cells (C-iEPCs) in vitro and in vivo. The bleeding phenotype was rescued in HA mice after C-iEPC infusion. Our results demonstrate an efficient approach for in situ gene correction via introduction of a tiny deletion using ssODN and CRISPR/Cas9 to reframe the F8 transcript and restore FVIII function in HA-iPSC-derived EPCs with potential clinical impact in HA gene therapy. For the first time, we demonstrated in vitro and in vivo the FVIII function that is encoded by the endogenous F8 gene with a partially deleted B domain. This work also suggests an applicable strategy for genetic correction of other gene frameshift mutations.

15.
ACS Appl Mater Interfaces ; 11(30): 26920-26927, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31268655

RESUMO

We report a three-dimensional (3D) garnet framework-reinforced solid composite electrolyte with enhanced Li-ion conductivity and excellent thermal, mechanical, and electrochemical stabilities. The 3D garnet framework is fabricated via the polymeric sponge method, using low-cost polyurethane foam as the template. The interconnected 3D garnet framework not only reinforces the composite electrolyte but also forms continuous Li-ion transport pathways, thereby increasing the ionic conductivity. The 3D garnet composite electrolyte shows an ionic conductivity of 1.2 × 10-4 S cm-1 at 30 °C, about two times as high as that of the garnet particle-reinforced composite electrolyte. The Li-Li symmetric cell based on the 3D garnet composite electrolyte can be cycled more than 360 h without short circuit, suggesting an improved ability to suppress Li-dendrites. The Li/3D garnet composite electrolyte/LiFePO4 battery demonstrates stable cycling performance at 0.5 C. Owing to the cost-saving characteristics, the 3D garnet-reinforced solid composite electrolyte is promising for mass production.

16.
Eur J Med Genet ; : 103709, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31229681

RESUMO

Oculocutaneous albinism is an autosomal recessive disorder characterized by either a complete lack of or reduction in melanin biosynthesis in the skin, hair, and eyes. The aim of the present study was to identify the molecular basis for 59 Chinese OCA families. In this study, compound heterozygous or homozygous pathogenic variants were found in 53 families, 4 families possessed only one heterozygous variant, and the pathogenic variants of 2 families remain undiscovered by using Sanger sequencing, whole exome sequencing and multiplex ligation-dependent probe amplification. We have identified a total of 55 variants including 21 novel variants in TYR, OCA2, SLC45A2, SLC24A5, and HPS1. The 21 novel variants include 11 missense changes, 4 nonsense changes, 2 splice site changes, 1 frameshift and 3 gross deletions. Forty-six variants including 14 novel variants were segregated with the phenotype in 37 families. We conducted RT-PCR of the novel splicing site variant (c.399-14G > A) of HPS1 and verified that the variant would result in the inclusion of 12 bp of intronic material in exon 6 of HPS1. The results of platelet whole mount electron microscopy further confirmed the diagnosis of HPS1. These novel variants identified in our study expand the mutational spectrum of the disease, which contributes to prenatal diagnosis and genetic counselling.

17.
Chem Pharm Bull (Tokyo) ; 67(8): 855-863, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31167984

RESUMO

A highly rapid and sensitive ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-TSQ-MS/MS) method was developed for the simultaneous determination of 7 constituents from Zaoren Anshen prescription (ZAP) and 4 endogenic components in rat plasma. The proteins in the plasma samples were removed using acetonitrile. The separation of the 11 components was performed on an Alltima C18 column (150 × 4.6 mm, 5 µm) with acetonitrile and 0.01% formic acid water as the mobile phase. Quantification of the 11 components was performed by multiple reaction monitoring (MRM), and the electrospray ion source polarity was switched between positive and negative modes. The method exhibited good linearity for the 11 components (R2 > 0.9942). The lower quantitative limit for the 11 components was in the range from 0.90-9.95 ng/mL. The precision was evaluated by intraday and interday assays, with all relative standard deviation (RSD)% values within 14.92%. The relative error of the accuracy ranged from -9.90 to 14.93%. The recovery ranged from 73.94 to 101.06%, and the matrix effects of the 7 components ranged from 80.06 to 105.70%. The developed method was successfully applied for correlation analysis for the simultaneous quantification of the 7 constituents from ZAP and 4 endogenic components in rat plasma after ZAP treatment.


Assuntos
Medicamentos de Ervas Chinesas/análise , Administração Intravenosa , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
19.
Se Pu ; 37(6): 626-633, 2019 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-31152513

RESUMO

A comprehensive analytical method was developed for the simultaneous determination of 14 sexual hormones in health care products by ultra performance liquid chromatography-atmospheric pressure chemical ionization-triple quadrupole mass spectrometry (UPLC-APCI-MS/MS). The samples were extracted twice with acetonitrile and the extracts were purified using hydrophilic-lipophilic balance (HLB) cartridges. Chromatographic separation was achieved on a Hypersil Gold C18 column (100 mm×2.1 mm, 1.9 µm) by gradient elution with acetonitrile and 10 mmol/L ammonium acetate aqueous solution as the mobile phases. Compounds were detected by APCI-MS/MS with external standard calibration curve method. All the 14 sexual hormones showed a good linear trend in their respective concentration ranges and the correlation coefficients (r) were no less than 0.996. The limits of detection (LODs) ranged from 0.0990 µg/kg to 2.09 µg/kg. The limits of quantification (LOQs) were in the range of 0.495-5.23 µg/kg. The average recoveries of the 14 sexual hormones in the health care product samples ranged from 65.8% to 118.8% at the three spiked levels. The precisions (n=6) ranged from 0.6% to 8.7% (n=6). The method is simple, sensitive, accurate and precise, and is suitable for the determination of the illegal added sexual hormones in the health care products.


Assuntos
Cosméticos/análise , Hormônios Esteroides Gonadais/análise , Pressão Atmosférica , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Limite de Detecção , Espectrometria de Massas em Tandem
20.
Medicine (Baltimore) ; 98(20): e15692, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096510

RESUMO

RATIONALE: Hereditary multiple exostoses (HMEs) is an autosomal dominant skeletal disorder. PATIENT CONCERNS: Six probands of the 6 unrelated Han Chinese families were identified as having HME. These patients had exostoses at multiple sites and significantly affected joints malformation and movement. DIAGNOSES: Hereditary multiple exostoses. INTERVENTIONS: To detect the genetic mechanism of HME in 6 unrelated Chinese families, whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) were used after genomic DNA was isolated from peripheral blood leucocytes. Point mutations identified by these methods were verified by Sanger sequencing after PCR amplification. OUTCOMES: Six mutations in the EXT1 and EXT2 genes were identified, including a heterozygous deletion mutation from exon 2 to exon 8 (Family 1), a c.448C>T, p.(Gln150X) heterozygous nonsense mutation (Family 4), a c.1057-2A>T heterozygous splicing substitution (Family 5), and a c.1468dupC, p.(Leu490fs519X) (Family 6) heterozygous duplication mutation in the EXT1 gene in addition to a heterozygous deletion mutation from exon 2 to exon 3 (Family 2) and a c.1197C>G, p.(Tyr399X) heterozygous nonsense mutation (Family 3) in the EXT2 gene. LESSONS: Overall, we identified 5 novel mutations and 1 recurrent mutation in the EXT1 and EXT2 genes in 6 Chinese families with HME. Our findings expand the mutational spectrum of the EXT1 and EXT2 genes and are useful for genetic counseling and prenatal diagnosis.


Assuntos
Exostose Múltipla Hereditária/diagnóstico , Exostose Múltipla Hereditária/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Mutação/genética , Sequenciamento Completo do Exoma/métodos , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Criança , Exostose Múltipla Hereditária/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , N-Acetilglucosaminiltransferases , Linhagem , Diagnóstico Pré-Natal/métodos
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