Publications by authors named "Ren Cai"

103 Publications

Expression of VEGF-A Signaling Pathway in Cartilage of ACLT-induced Osteoarthritis Mouse Model.

J Orthop Surg Res 2021 Jun 14;16(1):379. Epub 2021 Jun 14.

Laboratory for New Techniques of Restoration & Reconstruction of Orthopedics and Traumatology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.

Background: Anterior cruciate ligament transection surgery (ACLT)-induced OA model was often used to investigate the molecular mechanism of knee osteoarthritis (KOA). Researches have shown that vascular endothelial growth factor (VEGF) played an important role in OA. The present study aimed to investigate the pathological changes after ACLT surgery and reveal the expression characteristics of the VEGF-A/VEGFR2 signaling pathway in this model.

Methods: Moderate KOA model was established by ACLT, and 1, 2, 4, 8, and 12 weeks after surgery, hematoxylin-eosin (HE) and Safranin-O(S-O) staining were used to detect the pathological changes in mouse knee cartilage, and the matrix biomarkers A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5(ADAMTS5), Collagen II (COL-II) were detected using immunohistochemistry (IHC), CD31 was detected by immunofluorescence (IF) to show the vascular invasion in cartilage, and proteins expression of VEGF-A pathway were detected by Western blot (WB). Meanwhile, the inflammatory biomarkers cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cartilage were detected by WB.

Results: ACLT surgery can lead to degeneration of cartilage in mice, and the characteristics of the lesion were time-dependent. The ADAMTS5-positive cells increased while COL-II decreased in OA cartilage with time, and new blood vessels labeled by CD31 can be seen from 1 week in OA cartilage, and increased in 8 and 12 weeks. The expression of VEGF-A, VEGFR2, COX-2, and iNOS were higher than control groups, which were basically consistent with the degree of osteoarthritis.

Conclusions: The degenerative degree of articular cartilage was time-dependent; angiogenesis and inflammation were important pathological changes of cartilage in KOA. The expression of the VEGF-A/VEGFR2 signaling pathway was basically correlated with the degree of KOA.
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http://dx.doi.org/10.1186/s13018-021-02528-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201729PMC
June 2021

Aptamer-Pendant DNA Tetrahedron Nanostructure Probe for Ultrasensitive Detection of Tetracycline by Coupling Target-Triggered Rolling Circle Amplification.

ACS Appl Mater Interfaces 2021 May 21;13(17):19695-19700. Epub 2021 Apr 21.

Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, College of Material Science and Engineering, and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082, China.

Tetracycline (TET) is a broad-spectrum antibiotic, which is frequently used in the prevention and treatment of animal diseases, feed additives, and so on. However, its residue and accumulation in animal-derived foods could cause several side effects to the human body. Herein, we fabricated TET aptamer-pendant DNA tetrahedral nanostructure-functionalized magnetic beads (Apt-tet MBs) as a probe to detect TET. In the presence of target TET, DNA primer was released from Apt-tet MBs since the TET aptamer could specifically bind TET. Next, the separated DNA primer could effectively initiate rolling circle amplification (RCA) reaction and generate a long tandem single-stranded sequence. Finally, with SYBR Green I as the fluorescence dye, the fluorescence signal could be detected by detection probes through hybridizing the RCA product. Under optimal conditions, the fluorescent signal increased with the increasing target TET concentration within the 5 orders of magnitude dynamic range from 0.001 to 10 ng mL. The detection limit was calculated to be 0.724 pg mL and the method showed high selectivity toward TET among different antibiotics. More impressively, this method was employed for TET determination in fish and honey samples. The as-obtained results were consistent with those of ELISA kits, holding great potential in the field of food analysis.
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http://dx.doi.org/10.1021/acsami.1c02612DOI Listing
May 2021

A Hydrophobic Sisal Cellulose Microcrystal Film for Fire Alarm Sensors.

Nano Lett 2021 03 16;21(5):2104-2110. Epub 2021 Feb 16.

Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Material Science and Engineering, and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082, China.

At present, environmentally friendly biobased flexible films are of particular interest as next-generation fireproof packaging and sensor materials. To reduce the moisture uptake and fire risks induced by hygroscopic and flammable biobased films, we report a simple and green approach to develop a hydrophobic, flame-retardant composite film with synergetic benefit from soy protein isolate (SPI), sisal cellulose microcrystals (MSF--COOH), graphene nanosheets (GN), and citric acid (CA). Compared with SPI/MSF--COOH composite films, the as-prepared SPI/MSF--COOH/CA/GN composite films have significantly improved water resistance and can maintain excellent physical structure and good electrical conductivity in an ethanol flame. This work opens a pathway for the development of novel fire-retardant fire alarm biosensors.
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http://dx.doi.org/10.1021/acs.nanolett.0c04789DOI Listing
March 2021

Managing Vascular Anomalies in the Era of Genetics and Precision Medicine: An Opportunity or a Challenge?

Ann Plast Surg 2021 03;86(3S Suppl 2):S269-S272

From the Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital School of Medicine.

Abstract: The era of genetics and precision medicine has been reforming this world. How will plastic surgeons in the field of vascular anomalies conform to the trend? This article systematically reviews the identification of serum biomarkers, risk factors, specific mutations in the angiogenesis-related genes such as GNAQ, RASA1, TEK, and their impact on the diagnosis and treatment of vascular anomalies with preliminary results that have been previously reported and leading the tide. Moreover, a new disease classification for complex vascular malformations based on PIK3CA genetic evidence and various treatment breakthroughs is briefly summarized. With gene sequencing, bioinformatics, and big data, we confront the challenges of research in the vascular anomalies domain and explore possibilities of precision medicine development.
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http://dx.doi.org/10.1097/SAP.0000000000002723DOI Listing
March 2021

On-Site Colorimetric Detection of Cholesterol Based on Polypyrrole Nanoparticles.

ACS Appl Mater Interfaces 2020 Dec 25;12(49):54426-54432. Epub 2020 Nov 25.

Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Biology College of Material Science and Engineering, College of Chemistry and Chemical Engineering, and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082, China.

Herein, we report a facile method for cholesterol detection by coupling the peroxidase-like activity of polypyrrole nanoparticles (PPy NPs) and cholesterol oxidase (ChOx). ChOx can catalyze the oxidation of cholesterol to produce HO. Subsequently, PPy NPs, as a nanozyme, induce the reaction between HO and 3,3',5,5'-tetramethylbenzidine (TMB). Under optimal conditions, the increase is proportional to cholesterol with concentrations from 10 to 800 μM in absorbance of TMB at 652 nm. The linear range for cholesterol is 10-100 μM, with a detection limit of 3.5 μM. This reported method is successfully employed for detection of cholesterol in human serum. The recovery percentage is ranged within 96-106.9%. Furthermore, we designed a facile and simple portable assay kit using the proposed system, realizing the on-site semiquantitative and visual detection of cholesterol in human serum. The cholesterol content detected from the portable assay kit were closely matching those obtained results from solution-based assays, thereby holding great potential in clinical diagnosis and health management.
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http://dx.doi.org/10.1021/acsami.0c15900DOI Listing
December 2020

Human serum albumin templated MnO nanosheets as an efficient biomimetic oxidase for biomolecule sensing.

J Mater Chem B 2020 12;8(48):11090-11095

State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Materials Science and Engineering, Hunan University, Changsha 410082, China.

Herein, we have proposed a colorimetric biosensor for detection of acid phosphatase based on human serum albumin (HSA) templated MnO2 nanosheets (HSA-MnO2 NSs). HSA-MnO2 NSs as an efficient biomimetic oxidase could catalyze the oxidization of 3,3',5,5'-tetramethylbenzidine (TMB) to the coloured oxidation product (oxTMB). Acid phosphatase (ACP) could hydrolyze l-ascorbic acid-2-phosphate (AAP) to produce ascorbic acid, and ascorbic acid could lead to the decomposition of MnO2 NSs to Mn2+ ions, inhibiting the production of oxTMB. On the basis of this, we have demonstrated a novel colorimetric approach for the detection of acid phosphatase with the linear range from 50 μU mL-1 to 1500 μU mL-1 and a detection limit of 40 μU mL-1. The MnO2 NS-based colorimetric method has been successfully used to determine the content of acid phosphatase in real samples with satisfactory results.
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http://dx.doi.org/10.1039/d0tb01766cDOI Listing
December 2020

Highly Sensitive MicroRNA Detection by Coupling Nicking-Enhanced Rolling Circle Amplification with MoS Quantum Dots.

Anal Chem 2020 10 17;92(19):13588-13594. Epub 2020 Sep 17.

Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, College of Material Science and Engineering, and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082, China.

In this work, a label-free and highly sensitive fluorescence assay was constructed for microRNA detection. Nicking-enhanced rolling circle amplification (RCA) induced by G-quadruplex formation is coupled with inner filter effect (IFE)-based quenching effects of MoS quantum dots (MoS QDs). The padlock probe contains a recognition sequence to target microRNA and an accessible nicking site. The padlock probe is cyclized upon hybridization with target microRNA. Sequentially, amplification initiates a production of a long-concatenated sequence of circular probes. Abundant G-quadruplex sequences are produced the nicking process and then used as the trigger to initiate the next RCA. In the presence of hemin, numerous hemin/G-quadruplex DNAzymes are formed, which catalyze the oxidation of -phenylenediamine (OPD) into the colored product 2,3-diaminophenazine, resulting in quenching of the fluorescence of MoS QDs. This sensing strategy enables detection of microRNA let-7a with high selectivity and a detection limit of 4.6 fM. The as-prepared sensor was applied for detecting microRNA let-7a in dilute human serum samples and achieved a satisfactory recovery rate, demonstrating its potential in clinic diagnosis of microRNA-associated disease and biochemical research.
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http://dx.doi.org/10.1021/acs.analchem.0c03405DOI Listing
October 2020

NGS-based spinal muscular atrophy carrier screening of 10,585 diverse couples in China: a pan-ethnic study.

Eur J Hum Genet 2021 Jan 3;29(1):194-204. Epub 2020 Sep 3.

BGI Genomics, BGI-Shenzhen, 518083, Shenzhen, China.

In this study, we performed a spinal muscular atrophy carrier screening investigation with NGS-based method. First, the validation for NGS-based method was implemented in 2255 samples using real-time PCR. The concordance between the NGS-based method and real-time PCR for the detection of SMA carrier and patient were up to 100%. Then, we applied this NGS-based method in 10,585 self-reported normal couples (34 Chinese ethnic groups from 5 provinces in South China) for SMA carrier screening. The overall carrier frequency was 1 in 73.8 (1.4%). It varied substantially between ethnic groups, highest in Dai ethnicity (4.3%), and no significant difference was found between five provinces. One couple was detected as carriers with an elevated risk of having an SMA affected baby. The distribution of SMN1:SMN2 genotype was also revealed in this study. Among the individuals with normal phenotype, the exon 7 copy-number ratio of SMN1 to SMN2 proved the gene conversion between them. With NGS-based method, we investigated SMA carrier status in Chinese population for the first time, and our results demonstrated that it is a promising alternative for SMA carrier screening and could provide data support and reference for future clinical application.
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http://dx.doi.org/10.1038/s41431-020-00714-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852551PMC
January 2021

Novel genetic alteration in congenital melanocytic nevus: MAP2K1 germline mutation with BRAF somatic mutation.

Hereditas 2020 Aug 26;157(1):35. Epub 2020 Aug 26.

Department of Plastic and Reconstructive Surgery, Shanghai 9th Peoples Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.

Congenital melanocytic nevus (CMN) represent a benign proliferative skin disease in the epidermis and dermis. CMN are historically known to be associated with activating NRAS or BRAF mutations. Melanoma frequently harbors the BRAF p.Val600Glu mutation, which is also commonly found in benign nevi. A recent study reported mutation of MAP2K1, a downstream effector of the RAS-RAF-MEK pathway, in melanoma with an overall frequency of 8%. Later, in 2019, Jansen P detected one activating MAP2K1 mutation in acral nevi. However, it is unknown whether MAP2K1 mutations are common in CMN, and how MAP2K1 contributes to the pathogenesis of CMN remains to be determined.In this study, we report one patient clinically and histologically diagnosed with CMN, with the MAP2K1 germline mutation and a BRAF p.Val600Glu somatic hit in the lesion. To the best of our knowledge, this is the first report of the coexistence of mutated BRAF and MAP2K1 in CMN, which may suggest that MAP2K1 mutations contribute to the occurrence and development of nevus expanding our knowledge of the genetics of CMN.
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http://dx.doi.org/10.1186/s41065-020-00147-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449081PMC
August 2020

Pedigree Analysis of Nonhomologous Sequence Recombination of and Genes.

Hemoglobin 2020 Sep 19;44(5):329-333. Epub 2020 Aug 19.

Department of Medical Genetics, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, Guangxi Zhuang Autonomous Region, People's Republic of China.

The aim of this study was to investigate a family with nonhomologous sequence recombination of and genes and provide a favorable basis for genetic counseling and eugenics. Peripheral blood of family members was collected. Hematological parameters were determined by an automated cell counter and hemoglobin (Hb) analysis was performed using high performance liquid chromatography (HPLC). Villus samples were taken for prenatal diagnosis (PND). Gap-polymerase chain reaction (gap-PCR) and reverse dot-blot were used for thalassemia genotyping. DNA sequencing was used to analyze the gene sequence of (α1-globin) and (α2-globin). The nonhomologous sequence recombination allelic variant of and genes were identified, namely, a gene conversion on the gene called α12 (). The α12 allele consists primarily of the gene sequence except for a segment of the IVS-II in which -specific sequences have been replaced by -specific sequences. The following genotypes were observed: - -/αα12 (Southeast Asian deletion), αα/αα12 and αα/αα12 (Hb Quong Sze or Hb QS; : c.377T>C), and all manifested as small cell hypochromic anemia. To find the α12 allele in the Chinese population and clarify the influence of the α12 allele and its common inheritance with abnormal Hb and α-thalassemia (α-thal) on α-globin gene expression can help guide clinical diagnosis and genetic counseling.
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http://dx.doi.org/10.1080/03630269.2020.1807355DOI Listing
September 2020

Association between TP53 gene deletion and protein expression in esophageal squamous cell carcinoma and its prognostic significance.

Oncol Lett 2020 Aug 9;20(2):1855-1865. Epub 2020 Jun 9.

Department of Thoracic Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.

The aim of the present study was to investigate the association between tumor protein 53 () gene deletion and protein expression and clinical features in esophageal squamous cell carcinoma (ESCC), and to evaluate the predictive value of these two characteristics in the prognosis of ESCC. Immunohistochemistry (IHC) and fluorescence hybridization (FISH) were performed to detect the expression of p53 protein and gene deletion in ESCC tissue samples from different ethnic groups in Xinjiang, in order to analyze their association with clinicopathological characteristics and patient prognosis, as well as the sensitivity and specificity of the two methods. In addition, the results were further validated by tissue microarray from a different region. The positive rate of p53 protein expression was 54.5% (201/369) in the multi-ethnic group, and was significantly different between sex (P=0.026) and between tumor differentiation groups (P=0.032). FISH demonstrated that the gene deletion rate was 31.8% (68/214), which was significantly different between different tumor differentiation (P=0.002), lymph node metastasis (P=0.005) and vascular invasion (P<0.001) groups. The survival rate of patients with gene deletion was significantly lower than those without gene deletion (P<0.05). The positive rate of p53 protein expression in the tissue microarray was 58.1% (68/117), which was significantly different between the depth of invasion groups (P=0.011). The gene deletion rate was 47.9% (56/117), which significantly differed according to lymph node metastasis (P=0.003) and TNM stage (P=0.01). In addition, the total concordance rates of the two methods were 60.3 and 64.1%, respectively. There were also significant differences in the positive rate of gene deletion and protein expression in different stages of ESCC (P<0.05), which increased gradually with the progression of ESCC. The deletion of the gene in esophageal cancer was associated with poor prognosis and may be an important biomarker for evaluating the prognosis of patients with ESCC. The combination of FISH and IHC methods could significantly improve the detection rate of gene abnormalities and the accuracy of prognostic assessment of ESCC.
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http://dx.doi.org/10.3892/ol.2020.11709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377104PMC
August 2020

Aptamer-Directed Protein-Specific Multiple Modifications of Membrane Glycoproteins on Living Cells.

ACS Appl Mater Interfaces 2020 Aug 13;12(34):37845-37850. Epub 2020 Aug 13.

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.

Understanding how a cell membrane protein functions on living cells remains a challenge for cell biology. Specific placement of functional molecules on specific proteins in their native environment would allow comprehensive study of proteins' dynamic functions. Existing methods cannot facilely achieve multiple modifications on specific membrane proteins. In this report, we describe an aptamer-induced, protein-specific bio-orthogonal modification technology for precise nongenetic immobilization of multiple small functional molecules on target membrane glycoproteins by combining metabolic technology and aptamer targeting. In brief, DNA probes were designed by modifying aptamers, which bind to target proteins on the surfaces of living cells pretreated with -azidoacetylmannosamine-tetraacylated (AcManNAz). The cyclooctynes tagged of DNA probes will approach the azide groups to trigger the bio-orthogonal reactions. After UV irradiation and hybridization with cDNA (complementary DNA), the aptamers can be removed, and the process can be repeated to achieve multiple modifications for multicolor imaging and cell surface nanoengineering on specific proteins.
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http://dx.doi.org/10.1021/acsami.0c07004DOI Listing
August 2020

Unilateral and segmental distribution of facial erythema: is it a real port-wine stain?

Hereditas 2020 Jul 7;157(1):27. Epub 2020 Jul 7.

Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

Capillary malformation-arteriovenous malformations (CM-AVMs) caused by a RASA-1 or EPHB4 mutation are characterized as hereditary sporadic or multifocal capillary malformations (CMs), associated with potential fast-flow vascular anomalies underlying erythema lesions. Because of the similar phenotype, CM-AVMs should be considered in the differential diagnosis of isolated CMs as well as other disorders with an erythema phenotype, such as hereditary hemorrhagic telangiectasia (HHT).Herein, we report a male patient with facial erythema. Red lesions were located in the V1 region of his left face, the V2 and V3 regions on his right side, and the nasal back. The patient was initially thought to have PWSs because of the unilateral and segmental distribution of his red facial lesions. In contrast to a previous diagnosis, we diagnosed the child with capillary malformation-arteriovenous malformation type 2 (CM-AVM2) based on a family history of erythema, the results of physical examination and ultrasound raising potential fast-flow lesions, and a genetic study revealing a germline EPHB4 mutation. This study emphasizes the importance of differential diagnosis for PWS and CM-AVM. A single clinical diagnosis can be limited, and molecular diagnosis is recommended to provide more information for the evaluation of the potential risk of fast-flow lesions underlying erythema lesions if necessary.
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http://dx.doi.org/10.1186/s41065-020-00143-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341638PMC
July 2020

Giant congenital melanocytic nevus of the scalp: from clinical-histological to molecular diagnosis.

Hereditas 2020 May 19;157(1):21. Epub 2020 May 19.

Department of Plastic and Reconstructive Surgery, Shanghai 9th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

Congenital melanocytic nevus (CMN) is a benign proliferative skin disease in the epidermis and dermis. Large to giant CMNs are estimated to be associated with an increased lifetime risk of malignancy. It is necessary to estimate and monitor the risk of malignant transformation for giant CMNs. To date, the clinical "ABCD" criteria and immunohistochemistry studies can be confusing and, to some extent, subjective. Accordingly, the elucidation of genomic analyses of nevi is required to better understand the malignant transformation of CMNs. Here, we describe two large to giant CMNs of the scalp with opposite clinical-histological and molecular evaluations of potential malignancy risk. To our knowledge, this is the first description of a genetic study of large to giant CMNs of the scalp in East Asia. We recommend reviewing the molecular diagnosis together with careful medical history and histological information to facilitate the evaluation of the potential malignancy risk.
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http://dx.doi.org/10.1186/s41065-020-00133-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236929PMC
May 2020

Tumor microenvironment (TME)-activatable circular aptamer-PEG as an effective hierarchical-targeting molecular medicine for photodynamic therapy.

Biomaterials 2020 07 14;246:119971. Epub 2020 Mar 14.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau. Electronic address:

Photodynamic therapy (PDT) is an effective and noninvasive therapeutic strategy employing light-triggered singlet oxygen (SO) and reactive oxygen species (ROS) to kill lesional cells. However, for effective in vivo delivery of PDT agent into the cancer cells, various biological obstacles including blood circulation and condense extracellular matrix (ECM) in the tumor microenvironment (TME) need to be overcome. Furthermore, the enormous challenge in design of smart drug delivery systems is meeting the difference, even contradictory required functions, in different steps of the complicated delivery process. To this end, we present that TME-activatable circular pyrochlorophyll A (PA)-aptamer-PEG (PA-Apt-CHO-PEG) nanostructures, which combine the advantages of PEG and aptamer, would be able to realize efficient in vivo imaging and PDT. Upon intravenous (i.v.) injection, PA-Apt-CHO-PEG shows "stealth-like" long circulation in blood compartments without specific recognition capacity, but once inside solid tumor, PA-Apt-CHO-PEG nanostructures are cleaved and then form PA-Apt Aptamer-drug conjugations (ApDCs) in situ, allowing deep penetration into the solid tumor and specific recognition of cancer cells, both merits, considering anticipated future clinical translation of ApDCs.
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http://dx.doi.org/10.1016/j.biomaterials.2020.119971DOI Listing
July 2020

[Analysis of beta-globin gene variants in Liuzhou area of Guangxi].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Apr;37(4):378-383

Department of Medical Genetics, Liuzhou Maternal and Child Health Care Hospital, Liuzhou, Guangxi 545001, China.

Objective: To determine the composition and distribution of beta-thalassemia-associated genotypes in Liuzhou area of Guangxi, China.

Methods: From January to December 2017, 13 847 individuals who came for premarital examination, maternity examination or health check were recruited with informed consent. The subjects were analyzed by reverse dot blotting (RDB) for 17 common beta-thalassemia-associated variants among the Chinese population. Individuals with inconsistent results by blood test, electrophoresis, and RDB were subjected to Sanger sequencing to detect rare variants of the beta globin gene.

Results: In total 2098 individuals were found to harbor beta-thalassemia-associated variants, which included 2075 heterozygotes (98.90%), 12 compound heterozygotes (0.57%) and 11 homozygotes (0.52%). CD41-42 (48.43%) and CD17 (31.45%) were the most common variants. Three hundred and thirty eight-individuals were found to also carry heterozygous variants of the alpha globin gene, with the most common types being --SEA/aa, -a3.7/aa, aCSa/aa, -a4.2/aa. Through Sanger sequencing, rare genotypes such as beta-32/betaN, betaCD41-42/betaIVS-II-5 and betaCD30/betaN were detected.

Conclusion: Liuzhou area has a high incidence of beta-thalassemia, but with a complex variant spectrum and clinical phenotypes different from other regions. Genetic counseling and prenatal diagnosis for the carrier population is crucial for the reduction of the related birth defects. Our result may provide valuable information for the prevention and control of beta-thalassemia in this area.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.04.004DOI Listing
April 2020

Bleomycin Polidocanol Foam (BPF) Stability - In Vitro Evidence for the Effectiveness of a Novel Sclerosant for Venous Malformations.

Eur J Vasc Endovasc Surg 2020 Jun 14;59(6):1011-1018. Epub 2020 Feb 14.

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University, Shanghai, PR China. Electronic address:

Objective: This study investigated the in vitro stability of a novel sclerosant, bleomycin polidocanol foam (BPF), for venous malformation (VM) sclerotherapy.

Methods: The study was designed with control groups treated with polidocanol (0.5%, 1%, and 3%) only. The experimental groups included 21 BPFs, which was made by dissolving bleomycin at seven different concentrations (0.1%-1.5%) in polidocanol (0.5%, 1%, and 3%). The Tessari method was used to prepare sclerosant foam with a liquid:gas ratio of 1:4 at room temperature in vitro. The foam stability was measured for each group. The decay process, one component of foam stability, was recorded with a camera. Foam decay process experiments were performed 10 times per group. The stability indices included drainage rate, drainage time, half life, and microscopic measurement of the foams (mean bubble diameter, minimum and maximum bubble diameters, wall thickness, and bubble diameter distribution).

Results: Compared with the control groups, the half lives of BPFs mainly increased significantly with the addition of bleomycin (p < .001). BPF with 3% polidocanol and 0.1% bleomycin recorded the highest half life (246 ± 1.6 sec), and this group also achieved the smallest bubble diameter and wall thickness (69.9 μm and 5.80 μm) among the experimental groups. For the same polidocanol concentration, the bubble diameter and wall thickness increased when bleomycin was added.

Conclusion: Bleomycin concentrations account for different BPF stability. BPF stability mainly increased significantly with the addition of a small amount of bleomycin but this advantage was no longer apparent with increasing bleomycin dose.
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http://dx.doi.org/10.1016/j.ejvs.2020.01.023DOI Listing
June 2020

Spontaneous and Dramatic Improvements in Open Bite Deformity Secondary to Large Maxillofacial Venous Malformation With Macroglossia After Sclerotherapy and Laser Therapy.

J Craniofac Surg 2020 Mar/Apr;31(2):530-533

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Large maxillofacial venous malformation (VM) lesions can affect the craniofacial skeleton, causing occlusal and craniofacial deformity. Few studies have discussed the management of these skeletal disorders. It is unclear whether orthodontic treatment and orthognathic surgery are necessary after such a VM lesion has been significantly reduced.

Methods: A 13-year-old boy with a large, extensive maxillofacial VM lesion, severe facial asymmetry, macroglossia, and lower lip hypertrophy visited our department in 2010. He received more than 100 sclerotherapy treatments and 20 laser treatments in the past 8 years.

Results: The patient's cosmetic disfigurement greatly improved, and the VM lesion diminished by more than 80%. Changes in the bite and craniofacial skeleton progressed from "normal" to "open bite with skeletal deformity" and finally to "spontaneously close to normal".

Conclusions: During the progression of VM, removal of pathogenic factors can inhibit the aggravation of open bite deformity and promote the spontaneous improvement, thereby circumventing the need for complicated osteotomy, orthodontic intervention and/or orthognathic surgery.
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http://dx.doi.org/10.1097/SCS.0000000000006188DOI Listing
July 2020

Diagnosis and Prenatal Diagnosis in a Chinese Family Carrying the Rare α-Thalassemia Gene : c.1A>G Mutation.

Hemoglobin 2020 Jan 14;44(1):51-54. Epub 2020 Jan 14.

Department of Medical Genetics, Liuzhou Maternal and Child Health Hospital, Liuzhou, People's Republic of China.

The aim of this study was to identify the rare thalassemia genotype in a family and perform prenatal diagnosis (PND) on the proband's unborn child. Peripheral blood was collected from the family members for hematology analysis and capillary electrophoresis (CE) analysis. Peripheral blood and cord blood were analyzed by gap-polymerase chain reaction (gap-PCR), reverse dot-blot and Sanger sequencing for genotypes of α-thalassemia (α-thal). A heterozygous mutation, : c.1A>G, was identified in the proband and his father. Two compound heterozygous variants, : c.1A>G and the - - (Southeast Asian) deletion, were revealed in the proband's unborn child. The hemoglobin (Hb) CE result of the fetal cord blood indicated the fetus had Hb H disease. We have identified a rare thalassemia mutation (: c.1A>G) in a Chinese family and enriched the rare α-thal gene pool in the Chinese population. When the patient's phenotype does not match the genotype detected by thalassemia gene detection kits, further investigation of rare genotypes should be conducted to avoid missed diagnosis or misdiagnosis, which can help guide clinical diagnosis, population screening and genetic counseling.
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http://dx.doi.org/10.1080/03630269.2020.1711771DOI Listing
January 2020

[Analysis of PLA2G6 gene variant in a family affected with infantile neuroaxonal dystrophy].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Jan;37(1):21-24

Department of Medical Genetics, Liuzhou Maternal and Child Health Care Hospital, Liuzhou, Guangxi 545001, China.

Objective: To identify potential variant in a child diagnosed as infantile neuroaxonal dystrophy.

Methods: Genomic DNA was extracted from peripheral blood samples from the patient and his parents and subjected to next generation sequencing. Suspected variant was verified by PCR and Sanger sequencing. Pathogenicity of the mutation was predicted by using bioinformatic software including SIFT and PolyPhen-2.

Results: The child was found to carry compound heterozygous variations c.668C>A (p.Pro223Gln) and c.2266C>T (p.Gln756Ter) of the PLA2G6 gene, which were respectively inherited from his father and mother. c.2266C>T has changed codon 756 (glutamine) into a stop codon, resulting premature termination of peptide chain synthesis. c.2266C>T has not been reported previously and was predicted to be harmful.

Conclusion: The compound variants of c.668C>A (p.Pro223Gln) and c.2266C>T (p.Gln756Ter) of the PLA2G6 gene probably underlies the disease in the child. Above finding has enriched the variant spectrum of the PLA2G6 gene.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.01.006DOI Listing
January 2020

Characterization of two novel Alu element-mediated α-globin gene cluster deletions causing α-thalassemia by targeted next-generation sequencing.

Mol Genet Genomics 2020 Mar 2;295(2):505-514. Epub 2020 Jan 2.

Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, China.

α-thalassemia is an inherited blood disorder commonly caused by deletions or point mutations involving one or both α-globin genes. Recent studies shed new light on the critical role of upstream enhancers multi-species conserved sequences (MCSs) in the ordered regulation of α-globin gene expression. Herein, we reported two unrelated probands with deletions in α-globin genes and MCSs, respectively. The proband from Family A is a compound heterozygote carrying a known α mutation (-α) and a novel 60.2 kb deletion causing the absence of both α-globin genes. The proband from Family B, on the other hand, is a compound heterozygote with a known α mutation (--) and a novel deletion involving only upstream regulatory elements MCS-R1, R2 and R3, while the α-globin genes remain intact. Notably, both these two patients suffered varied extent of anemia, indicating that the loss of enhancer elements could equally lead to reduced synthesis of α-globin. Upon these observations, we then confirmed the exact breakpoints of these two novel deletions using a targeted next-generation sequencing (NGS) previously established by our group, which may enable further elucidation of the rearrangement mechanisms on these deletions and functional dissection of MCSs. Taken together, our study reports a reliable NGS-based molecular screening approach for accurate identification of copy number variations (CNVs) in the α-globin cluster and the genetic diagnosis of these two probands may help to extend the spectrum of α-thalassemia mutations in Chinese population.
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http://dx.doi.org/10.1007/s00438-019-01637-wDOI Listing
March 2020

[Analysis of P gene variations among fourteen patients with oculocutaneous albinism type II].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Dec;36(12):1163-1166

Department of Medical Genetics, Liuzhou Maternal and Child Health Care Hospital, Liuzhou, Guangxi 545001, China.

Objective: To analyze variations of TYR and P genes among 14 patients with clinically diagnosed oculocutaneous albinism.

Methods: Potential variations of the TYR and P genes were detected by Sanger sequencing. Novel variations were predicted with bioinformatics software including SIFT and PolyPhen-2.

Results: No variation was found in the TYR gene, while 9 types of variations were found in the P gene among the 14 patients, which included c.803-3C>G (7/26), c.1327G>A (p.Val443Ile) (5/26), c.632C>T (p.Pro211Leu) (4/26), c.1832T>C (p.Leu611Pro) (3/26), c.1349C>A (p.Thr450Lys) (2/26), c.2363C>T (p.Ser788Leu) (2/26), c.2228C>T (p.Pro743Leu) (1/26), c.1525A>G (p.Thr509Ala) (1/26), and c.1349C>T (p.Thr450Met) (1/26). Only 1 heterozygous variation was detected in 2 families. c.2363C>T (p.Ser788Leu), c.1832T>C (p.Leu611Pro) and c.1525A>G (p.Thr509Ala) were not reported previously and predicted as "harmful" to the protein function.

Conclusion: The main type of ocular albinism is oculocutaneous albinism type II in Liuzhou region, where the most common variations of the P gene were c.803-3C>G and c.1327G>A (p.Val443Ile). Above finding has enriched the variation spectrum of the P gene.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.12.003DOI Listing
December 2019

Association between lncRNA and GCKR gene in type 2 diabetes mellitus.

Clin Chim Acta 2020 Feb 20;501:66-71. Epub 2019 Nov 20.

Xinjiang Key Laboratory of Metabolic Disease, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang 830054, China. Electronic address:

Objective: To screen long non-coding RNA (lncRNA) related to glucokinase regulatory protein gene (GCKR), its differential expression was analyzed in patients with Type 2 diabetes mellitus (T2DM) and control samples. The correlation of lncRNA with GCKR was verified and its potential value as a molecular marker of T2DM was assessed.

Methods: Lymphocyte RNA was extracted from five patients with T2DM and five patients with non-T2DM. The expression profiles of circulating lncRNAs and mRNAs were obtained by microarray. Bioinformatics analysis was used to screen lncRNAs associated with the GCKR gene in 127 patients with T2DM and 130 patients with non-T2DM were selected. The expression levels of the GCKR gene and lncRNA (ENST00000588707.1 and TCONS_00004187) in the T2DM group and control group were verified by real-time PCR. Additionally, a correlation analysis was conducted. The value of circulating ENST00000588707.1 and TCONS_00004187 as biomarkers for the diagnosis of T2DM was performed by receiver operating characteristic curve analysis.

Results: We identified 68 lncRNAs and 74 mRNAs differentially expressed from the expression profile. Compared with the control group, the expression levels of the GCKR gene and lncRNA ENST00000588707.1 and TCONS_00004187 in the T2DM group were significantly lower (P < 0.05). The correlation analysis revealed that ENST00000588707.1 and TCONS_00004187 were correlated with GCKR gene expression and glycolipid metabolism (P < 0.05). ROC analysis showed that the area under the curve value of ENST00000588707.1 between T2DM patients and non-T2DM patients was 0.816 (95% CI: 0.764-0.869, sensitivity 72.0%, specificity 80.3%) and the AUC value of TCONS_00004187 was 0.826 (95% CI: 0.774-0.879, sensitivity 81.6%, specificity 61.3%).

Conclusion: lncRNA ENST0000588707.1 and TCONS_00004187 could serve as potential biomarkers for T2DM, which could involve in glycolipid metabolism by regulating the GCKR gene.
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http://dx.doi.org/10.1016/j.cca.2019.10.004DOI Listing
February 2020

[Tandem mass spectrometry analysis and genetic diagnosis of neonates with fatty acid oxidation disorders in central and northern regions of Guangxi].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Nov;36(11):1067-1072

Department of Medical Genetics, Liuzhou Maternal and Child Health Hospital, Liuzhou, Guangxi 545001,

Objective: To determine the incidence and mutational types of fatty acid oxidation disorders (FAOD) in central-northern region of Guangxi.

Methods: A total of 62 953 neonates were screened for FAOD during December 2012 and December 2017. Acyl-carnitine profiling of neonatal blood sample was performed by tandem mass spectrometry using dry blood spots on a filter paper. The diagnosis of FAOD was confirmed by organic acid profiling of urea and genetic testing.

Results: Eighteen cases of FAOD were diagnosed among the 62 953 neonates. Among these, primary carnitine deficiency (PCD) was the most common type (n=13), which was followed by short-chain acyl-CoA dehydrogenase deficiency (SCADD) (n=2), medium-chain acyl-CoA dehydrogenase deficiency (MCADD) (n=1), multiple acyl-CoA dehydrogenase deficiency (MADD) (n=1), and carnitine palmitoyltransferase II deficiency (CPT II D) (n=1). Genetic testing has revealed two previously unreported variants, i.e., c.337G to A (p.Gly113Arg) of ACADS gene and c.737G TO T (p.Gly246Val) of ETFA gene.

Conclusion: PCD is the most common FAOD in central-northern Guangxi. Tandem mass spectrometry combined with genetic testing may facilitate early diagnosis of FAOD.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.11.003DOI Listing
November 2019

3D halos assembled from FeO/Au NPs with enhanced catalytic and optical properties.

Nanoscale 2019 Nov 29;11(43):20968-20976. Epub 2019 Oct 29.

Molecular Sciences and Biomedicine Laboratory (MBL), State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering and College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, China. and Institute of Molecular Medicine (IMM), State Key Laboratory of Oncogenes and Related Genes Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China and Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, FL 32611-7200, USA.

3D structures assembled from multiple components have attracted increasing research interest based on their enriched functionalities and broadened applications. Here, we report a bottom-up strategy to fabricate 3D halos through the co-assembly of FeO and Au nanoparticles (NPs). Typically, FeO NPs assemble into a 3D core (size around 500 nm) with simultaneous growth of Au NPs on the 3D surface during the assembly process. As a general approach, a variety of 3D halos were fabricated from the co-assembly of FeO and Au NPs of different sizes and shapes. To demonstrate the advantages of these 3D halo structures, their catalytic activity to mimic natural enzymes was investigated. Compared with FeO NP building blocks, enhanced catalytic efficiency was achieved by the 3D halos. In addition, the optical behavior of the 3D halos was simulated using a three-dimensional finite-difference time-domain (3D-FDTD) method. As shown in the results, the 3D halos attached to 90 nm Au NPs could absorb more incident light owing to high electric field intensities, making these structures promising for applications in energy harvesting and detection-related fields.
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http://dx.doi.org/10.1039/c9nr05874eDOI Listing
November 2019

[Analysis of CGDH gene variants and clinical features in three patients with glutaric aciduria type Ⅰ].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Sep;36(9):882-885

Department of Medical Genetics, Liuzhou Maternal and Child Health Care Hospital, Liuzhou, Guangxi 545001, China.

Objective: To screen for potential variants of GCDH gene in 3 patients clinically diagnosed as glutaric aciduria type Ⅰ.

Methods: GCDH gene variants was detected by Sanger sequencing among the three children and their family members.

Results: Sanger sequencing showed that patient 1 carried compound heterozygosity variants of c.532G>A (p.Gly178Arg) and c.655G>A (p.Ala219Thr) of the GCDH gene, while his father and mother respectively carried heterozygous c.532G>A(p.Gly178Arg) and c.655G>A (p.Ala219Thr) variants. Patient 2 carried c.532G>A (p.Gly178Arg) and a novel c.1060G>T (p.Gly354Cys) compound heterozygous variant, while his father and mother respectively carried heterozygous c.532G>A (p.Gly178Arg) and c.1060G>T (p.Gly354Cys) variant. Patient 3 carried homozygous c.532G>A (p.Gly178Arg) variant of the GCDH gene, for which both of his parents were heterozygous carriers.

Conclusion: The GCDH gene variant probably underlie the glutaric aciduria type Ⅰ among the 3 patients. Identifcation of the novel variant has enriched the spectrum of GCDH gene variants.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.09.007DOI Listing
September 2019

Chinese newborn screening for the incidence of G6PD deficiency and variant of G6PD gene from 2013 to 2017.

Hum Mutat 2020 01 23;41(1):212-221. Epub 2019 Sep 23.

Dongguan Newborn Screening Center, Dongguan Maternal & Infant Health Hospital, Dongguan, Guangdong, China.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. We aimed to provide the characteristics of G6PD deficiency and G6PD gene variant distribution in a large Chinese newborn screening population. We investigated the prevalence of G6PD in China from 2013 to 2017. Then, we examined G6PD activity and G6PD gene in representative Chinese birth cohort to explore the distribution of G6PD gene variant in 2016. We then performed multicolor melting curve analysis to classify G6PD gene variants in 10,357 neonates with activity-confirmed G6PD deficiency, and DNA Sanger sequencing for G6PD coding exons if hot site variants were not found. The screened population, organizations, and provinces of G6PD deficiency were increased from 2013 to 2017 in China. The top five frequency of G6PD gene variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, and c.871G>A and varied in different provinces, with regional and ethnic features, and four pathogenic variant sites (c.152C>T, c.290A>T, c.697G>C, and c.1285A>G) were first reported. G6PD deficiency mainly occurs in South China, and the frequency of G6PD gene variant varies in different regions and ethnicities.
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http://dx.doi.org/10.1002/humu.23911DOI Listing
January 2020

[Analysis of TRPM6 gene variant in a pedigree affected with hypocalcemia secondary to hypomagnesemia].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Aug;36(8):805-808

Department of Medical Genetics, Liuzhou Maternal and Child Health Care Hospital, Liuzhou, Guangxi 545001, China.

Objective: To explore the molecular pathogenesis for a pedigree affected with hypocalcemia secondary to hypomagnesemia.

Methods: Sanger sequencing was used to detect potential variant of the TRPM6 gene in the patient and their parents.

Results: The results showed that the patient has carried novel homozygous c.3311C>T (p.Pro1104Leu) variant of the TRMP6 gene, for which both of his parents were heterozygous carriers. Analysis of protein functions using software predicted high risk of pathogenicity.

Conclusion: The homozygous c.3311C>T (p.Pro1104Leu) variant of the TRPM6 gene probably underlies the disease in this patient.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.08.013DOI Listing
August 2019

[SLC22A5 gene mutation analysis and prenatal diagnosis for a family with primary carnitine deficiency].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Jul;36(7):690-693

Department of Medical Genetics, Liuzhou Maternal and Child Health Care Hospital, Liuzhou, Guangxi 545001, China.

Objective: To carry out mutation analysis and prenatal diagnosis for a family affected with primary carnitine deficiency.

Methods: Genomic DNA of the proband was extracted from peripheral blood sample 10 days after birth. The 10 exons and intron/exon boundaries of the SLC22A5 gene were subjected to PCR amplification and Sanger sequencing. The proband's mother was pregnant again two years after his birth. Fetal DNA was extracted from amniocytes and subjected to PCR and Sanger sequencing.

Results: Tandem mass spectrometric analysis of the proband revealed low level of plasma-free carnitine whilst organic acids in urine was normal. Compound heterozygous SLC22A5 mutations c.1195C>T (inherited from his father) and c.517delC (inherited from his mother) were detected in the proband. Prenatal diagnosis has detected no mutation in the fetus. The plasma-free carnitine was normal after birth.

Conclusion: Appropriate genetic testing and prenatal diagnosis can prevent further child with carnitine deficiency. The identification of c.517delC, a novel mutation, enriched the spectrum of SLC22A5 mutations.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.07.008DOI Listing
July 2019

LOVD-DASH: A comprehensive LOVD database coupled with diagnosis and an at-risk assessment system for hemoglobinopathies.

Hum Mutat 2019 12 11;40(12):2221-2229. Epub 2019 Sep 11.

Department of Medical Genetics, Southern Medical University, Guangzhou, Guangdong, China.

Hemoglobinopathies are the most common monogenic disorders worldwide. Substantial effort has been made to establish databases to record complete mutation spectra causing or modifying this group of diseases. We present a variant database which couples an online auxiliary diagnosis and at-risk assessment system for hemoglobinopathies (DASH). The database was integrated into the Leiden Open Variation Database (LOVD), in which we included all reported variants focusing on a Chinese population by literature peer review-curation and existing databases, such as HbVar and IthaGenes. In addition, comprehensive mutation data generated by high-throughput sequencing of 2,087 hemoglobinopathy patients and 20,222 general individuals from southern China were also incorporated into the database. These sequencing data enabled us to observe disease-causing and modifier variants responsible for hemoglobinopathies in bulk. Currently, 371 unique variants have been recorded; 265 of 371 were described as disease-causing variants, whereas 106 were defined as modifier variants, including 34 functional variants identified by a quantitative trait association study of this high-throughput sequencing data. Due to the availability of a comprehensive phenotype-genotype data set, DASH has been established to automatically provide accurate suggestions on diagnosis and genetic counseling of hemoglobinopathies. LOVD-DASH will inspire us to deal with clinical genotyping and molecular screening for other Mendelian disorders.
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http://dx.doi.org/10.1002/humu.23863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899610PMC
December 2019
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