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Wang D.,CAS Guangzhou Institute of Biomedicine and Health | Ge C.,Guangzhou KingMed Center for Clinical Laboratory Co. | Wang L.,CAS Guangzhou Institute of Biomedicine and Health | Xing X.,CAS Tianjin Institute of Industrial Biotechnology | Zeng L.,CAS Guangzhou Institute of Biomedicine and Health
RSC Advances | Year: 2015

Copper(ii) ions (Cu2+) at a high concentration are harmful to human health. Herein a simple and enzyme-free lateral flow biosensor for the rapid detection of Cu2+ based on copper(i) ion (Cu+)-catalyzed click chemistry has been constructed for the first time. In the presence of sodium ascorbate, Cu2+ was reduced to Cu+, which could catalyze the cycloaddition between azide-DNA and alkyne/biotin-DNA in aqueous solution. The ligated DNA product could then be immobilized onto the test zone of the lateral flow biosensor to form a red band which could be unambiguously read by the naked eye. Taking advantage of the optical properties of gold nanoparticles (AuNPs) and high efficiency and selectivity of Cu+-catalyzed click chemistry, this assay enabled the visual detection of Cu2+ as low as 100 nM with excellent specificity. In comparison with conventional methods, this biosensor is more simple to operate and more cost-effective to use, and therefore has great potential in point-of-care diagnosis and environmental monitoring. © The Royal Society of Chemistry 2015.


PubMed | Russian Research Institute of Hematology and Transfusiology, University of Houston, Hospital Britanico, Jagiellonian University and 11 more.
Type: Journal Article | Journal: The Lancet. Haematology | Year: 2016

Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib.We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries). Eligible patients were aged 18 years or older with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase and Eastern Cooperative Oncology Group performance status of 0-2. Before enrolment, all patients had received 3-18 months of imatinib 400 mg once daily and had a suboptimal cytogenetic response according to 2009 ELN recommendations, established through bone marrow cytogenetics. By use of an interactive response technology using fixed blocks, we randomly assigned patients (1:1) to switch to nilotinib 400 mg twice per day or an escalation of imatinib dose to 600 mg once per day (block size of 4). Investigators and participants were not blinded to study treatment. Crossover was allowed for loss of response or intolerance at any time, or for patients with no complete cytogenetic response at 6 months. The primary endpoint was complete cytogenetic response at 6 months in the intention-to-treat population. Efficacy endpoints were based on the intention-to-treat population, with all patients assessed according to the treatment group to which they were randomised (regardless of crossover); the effect of crossover was assessed in post-hoc analyses, in which responses achieved after crossover were excluded. We present the final results at 24 months follow-up. This study is registered with ClinicalTrials.gov (NCT00802841).Between July 7, 2009, and Aug 29, 2012, we enrolled 191 patients. 96 patients were randomly assigned to nilotinib and 95 patients were randomly assigned to imatinib. Complete cytogenetic response at 6 months was achieved by 48 of 96 patients in the nilotinib group (50%, 9518% CI 40-61) and 40 of 95 in the imatinib group (42%, 32-53%; difference 79% in favour of nilotinib; 95% CI -62 to 220, p=031). Excluding responses achieved after crossover, 48 (50%) of 96 patients in the nilotinib group and 34 (36%) of 95 patients in the imatinib group achieved complete cytogenic response at 6 months (nominal p=0058). Grade 3-4 non-haematological adverse events occurring in more than one patient were headache (nilotinib group, n=2 [2%, including 1 after crossover to imatinib]; imatinib group, n=1 [1%]), blast cell crisis (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%]), and QT prolongation (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%, after crossover to nilotinib]). Serious adverse events on assigned treatment were reported in 11 (11%) of 96 patients in the nilotinib group and nine (10%) of 93 patients in the imatinib group. Seven (7%) of 96 patients died in the nilotinib group and five (5%) of 93 patients died in the imatinib group; no deaths were treatment-related.While longer-term analyses are needed to establish whether the clinical benefits observed with switching to nilotinib are associated with improved long-term survival outcomes, our results suggest that patients with suboptimal cytogenetic response are more likely to achieve improved cytogenetic and molecular responses with switching to nilotinib than with imatinib dose escalation, although the difference was not statistically significant when responses achieved after crossover were included.Novartis Pharmaceuticals.


Yuan H.,Guangzhou KingMed Center for Clinical Laboratory Co. | Yuan H.,Guangzhou University | Huang L.,Sun Yat Sen University | Hu X.,Fairmont Preparatory Academy | And 5 more authors.
Orphanet Journal of Rare Diseases | Year: 2016

Background: Achondroplasia is a well-defined and common bone dysplasia. Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations. Result: A 2-year-old boy with clinical features consistent with achondroplasia and Silver-Russell syndrome-like symptoms was found to carry a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene at c.1138G > A (p.Gly380Arg) and a de novo 574 kb duplication at chromosome 7p12.1 that involved the entire growth-factor receptor bound protein 10 (GRB10) gene. Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient. Conclusions: We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects. © 2016 The Author(s).


Yuan H.,Guangzhou Kingmed Center for Clinical Laboratory Co. | Yuan H.,Guangzhou University | Meng Z.,Sun Yat Sen University | Liu L.,Wuhan Women and Children Medical Healthcare Center | And 3 more authors.
Molecular Cytogenetics | Year: 2016

Backgroud: Microdeletions at 19q13.2 are very rare. Only two cases have been previously described. Here we report a 2-year-2-month old boy with Diamond-Blackfan anemia, global developmental delay, cognitive impairments, distinctive facial features, behavior problems, skeletal and genital dysplasia. Case presentation: A de novo 1.6 Mb microdeletion at 19q13.2q13.31 was detected by chromosomal microarray analysis. Haploinsufficiency of the RPS19 gene is known to cause Diamond-Blackfan anemia, other features in this patient are likely due to the deletion of other candidate genes such as PAFAH1B3, ERF, LIPE and GSK3A. Conclusion: The deletion detected in our patient overlapped and was significantly smaller than the ones previously reported, which offered the opportunity to further define the critical region for this proposed contiguous gene deletion syndrome. © 2016 The Author(s).


Yuan H.,Guangzhou Kingmed Center for Clinical Laboratory Co. | Yuan H.,Guangzhou University | Meng Z.,Sun Yat Sen University | Zhang L.,Sun Yat Sen University | And 7 more authors.
Molecular Cytogenetics | Year: 2016

Background: Interstitial duplications distal to 15q13 are very rare. Case Presentation: Here, we reported a 14-year-old boy with severe short stature, delayed bone age, hypogonadism, global developmental delay and intellectual disability. His had distinctive facial features including macrocephaly, broad forehead, deep-set and widely spaced eyes, broad nose bridge, shallow philtrum and thick lips. A de novo 6.4 Mb interstitial duplication of 15q15.3q21.2 was detected by chromosomal microarray analysis. We compared our patient's clinical phenotypes with those of several individuals with overlapping duplications and several candidate genes responsible for the phenotypes were identified as well. Conclusion: The results suggest a novel contiguous gene duplication syndrome characterized with shared features including short stature, hypogonadism, global developmental delay and other congenital anomalies. © 2016 Yuan et al.


Yuan H.,Guangzhou Kingmed Center for Clinical Laboratory Co. | Yuan H.,Guangzhou University | Zhang L.,Sun Yat Sen University | Chen M.,Guangzhou Kingmed Center for Clinical Laboratory Co. | And 3 more authors.
Molecular Cytogenetics | Year: 2015

Background: Mowat-Wilson syndrome (MWS) is a genetic condition characterized by distinctive facial features, moderate to severe intellectual disability, developmental delay and multiple congenital anomalies. MWS is caused by heterozygous mutations or deletions of the ZEB2 gene located on chromosome 2q22.3. At present, over 190 cases with mutations and deletions involving the ZEB2 gene have been reported, but triplication or duplication of reciprocal region of Mowat-Wilson syndrome has never been reported. Case Presentation: Here we report a 2-year-2-month-old boy carrying a de novo 2.9 Mb complex copy number gain at 2q22.3 involving triplication of ZEB2 gene. The boy is characterized by intrauterine growth retardation, hypotonia, cognitive impairment, multiple congenital anomalies and behavioral abnormalities. Conclusion: This case provides evidence that triplication of ZEB2 gene may be clinical significance and ZEB2 gene is likely to be a dosage sensitive gene. © 2015 Yuan et al.


PubMed | Guangzhou kingmed center for clinical laboratory Co., Guangzhou University and Sun Yat Sen University
Type: | Journal: Molecular cytogenetics | Year: 2015

Mowat-Wilson syndrome (MWS) is a genetic condition characterized by distinctive facial features, moderate to severe intellectual disability, developmental delay and multiple congenital anomalies. MWS is caused by heterozygous mutations or deletions of the ZEB2 gene located on chromosome 2q22.3. At present, over 190 cases with mutations and deletions involving the ZEB2 gene have been reported, but triplication or duplication of reciprocal region of Mowat-Wilson syndrome has never been reported.Here we report a 2-year-2-month-old boy carrying a de novo 2.9Mb complex copy number gain at 2q22.3 involving triplication of ZEB2 gene. The boy is characterized by intrauterine growth retardation, hypotonia, cognitive impairment, multiple congenital anomalies and behavioral abnormalities.This case provides evidence that triplication of ZEB2 gene may be clinical significance and ZEB2 gene is likely to be a dosage sensitive gene.


Lu J.,Central South University | Mo G.,Guangzhou Kingmed Center for Clinical Laboratory Co. | Ling Y.,Central South University | Ji L.,Central South University
Molecular Medicine Reports | Year: 2016

Kabuki syndrome (KS) is a rare genetic syndrome characterized by multiple congenital anomalies and varying degrees of mental retardation. Patients with KS often present with facial, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies and immunological defects. Mutation of the lysine methyltransferase 2D (KMT2D) gene (formerly known as MLL2) is the primary cause of KS. The present study reported the case of a 4-year-old Chinese girl who presented with atypical KS, including atypical facial features, unclear speech and suspected mental retardation. A diagnosis of KS was confirmed by genetic testing, which revealed a nonsense mutation in exon 16 of KMT2D (c.4485C>A, Tyr1495Ter). To the best of our knowledge, this is a novel mutation that has not been reported previously. The present case underscores the importance of genetic testing in KS diagnosis.


PubMed | Guangzhou Kingmed Center for Clinical Laboratory Co. and Central South University
Type: Journal Article | Journal: Molecular medicine reports | Year: 2016

Kabuki syndrome (KS) is a rare genetic syndrome characterized by multiple congenital anomalies and varying degrees of mental retardation. Patients with KS often present with facial, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies and immunological defects. Mutation of the lysine methyltransferase2D (KMT2D) gene (formerly known as MLL2) is the primary cause of KS. The present study reported the case of a 4yearold Chinese girl who presented with atypical KS, including atypical facial features, unclear speech and suspected mental retardation. A diagnosis of KS was confirmed by genetic testing, which revealed a nonsense mutation in exon16 of KMT2D (c.4485C>A, Tyr1495Ter). To the best of our knowledge, this is a novel mutation that has not been reported previously. The present case underscores the importance of genetic testing in KS diagnosis.


PubMed | Guangzhou KingMed Center for Clinical Laboratory Co.
Type: Journal Article | Journal: Cytogenetic and genome research | Year: 2016

Paternal uniparental disomy 14 (patUPD14) is a distinct, clinically recognizable syndrome. Using a clinical SNP microarray, we identified patUPD14 in a boy with a normal karyotype presenting cardiomyopathy and facial anomalies, a specific configuration of the thoracic ribs (coat hanger sign), and hypospadias. Analyses of polymorphic microsatellites confirmed the diagnosis of patUPD14. We discuss the functions of the genes included in the rearrangement and their involvement in the pathogenesis of these disorders, especially hypospadias. ESR2 single nucleotide polymorphisms (rs944050; 2681-4A>G) have been associated with an increased risk of hypospadias in previous studies. The patients ESR2 (rs944050) genotype is GG, whereas the parents both exhibit an AG genotype. This report sheds light on the genetic phenomenon in which the combination of a polymorphism and UPD can lead to new phenotypes, such as hypospadias.

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