Hongyan Wang

Fudan University, Shanghai, Shanghai Shi, China

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Publications (27)78.63 Total impact

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    ABSTRACT: Copy Number Variations (CNVs) are usually inferred from Single Nucleotide Polymorphism (SNP) arrays by use of some software packages based on given algorithms. However, there is no clear understanding of the performance of these software packages; it is therefore difficult to select one or several software packages for CNV detection based on the SNP array platform.We selected four publicly available software packages designed for CNV calling from an Affymetrix SNP array, including Birdsuite, dChip, Genotyping Console (GTC) and PennCNV. The publicly available dataset generated by Array-based Comparative Genomic Hybridization (CGH), with a resolution of 24 million probes per sample, was considered to be the "gold standard". Compared with the CGH-based dataset, the success rate, average stability rate, sensitivity, consistence and reproducibility of these four software packages were assessed compared with the "gold standard". Specially, we also compared the efficiency of detecting CNVs simultaneously by two, three and all of the software packages with that by a single software package. Simply from the quantity of the detected CNVs, Birdsuite detected the most while GTC detected the least. We found that Birdsuite and dChip had obvious detecting bias. And GTC seemed to be inferior because of the least amount of CNVs it detected. Thereafter we investigated the detection consistency produced by one certain software package and the rest three software suits. We found that the consistency of dChip was the lowest while GTC was the highest. Compared with the CNVs detecting result of CGH, in the matching group, GTC called the most matching CNVs, PennCNV-Affy ranked second. In the non-overlapping group, GTC called the least CNVs. With regards to the reproducibility of CNV calling, larger CNVs were usually replicated better. PennCNV-Affy shows the best consistency while Birdsuite shows the poorest. We found that PennCNV outperformed the other three packages in the sensitivity and specificity of CNV calling. Obviously, each calling method had its own limitations and advantages for different data analysis. Therefore, the optimized calling methods might be identified using multiple algorithms to evaluate the concordance and discordance of SNP array-based CNV calling.
    BMC Bioinformatics 02/2014; 15(1):50. · 3.02 Impact Factor
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    ABSTRACT: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, absence or delay in language development, and stereotyped or repetitive behaviors. Genetic studies show that neurexin-neuroligin (NRXN-NLGN) pathway genes contribute susceptibility to ASD, which include cell adhesion molecules , and scaffolding proteins and . Neuroligin proteins play an important role in synaptic function and trans-synaptic signaling by interacting with presynaptic neurexins. Shank proteins are scaffolding molecules of excitatory synapses, which function as central organizers of the postsynaptic density. Sequence level mutations and structural variations in these genes have been identified in ASD cases, while few studies were performed in Chinese population. In this study, we examined the copy numbers of four genes and in 285 ASD cases using multiplex fluorescence competitive polymerase chain reaction (PCR). We also screened the regulatory region including the promoter region and 5'/3' untranslated regions (UTR) and the entire coding region of in a cohort of 285 ASD patients and 384 controls by direct sequencing of genomic DNA using the Sanger method. DNA copy number calculation in four genes showed no deletion or duplication in our cases. No missense mutations in were identified in our cohort. Association analysis of 6 common SNPs in did not find significant difference between ASD cases and controls. These findings showed that these genes may not be major disease genes in Chinese ASD cases.
    PLoS ONE 01/2013; 8(2):e56639. · 3.53 Impact Factor
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    ABSTRACT: Crosslinked fluorinated polyimides (CFPI) were successfully synthesized to study and explore the effect of cross-linkage on the migration of fluorinated segments and on the adhesion strength. Characterization by dynamic thermomechanical analysis (DMA) and thermo gravimetric analysis (TGA) confirmed good thermal properties of CFPI. X-ray photoelectron spectroscopy (XPS) results showed that the ratio of fluorinated component (6FDA-ODA) concentration of the surface to the bulk decreased with the crosslink density. The water contact angle of CFPI was lower than that of non-crosslinked fluorinated polyimide, indicating that the migration of fluorinated groups to the surface was reduced by the presence of cross-linkage. Therefore, CFPI, with no fluorine segregation on the surface, exhibited excellent wetting of adherent surfaces and adhesion strength, which was proved by lap shear strength (LSS) measurements and scanning electron microscopy.
    Journal of Macromolecular Science Part B 01/2013; 52(7). · 0.63 Impact Factor
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    ABSTRACT: SMAD7 is a general antagonist of TGF-β signaling and has been found to be involved in cardiogenesis in mouse models, but its role in human congenital heart disease (CHD) has yet to be investigated. To examine if SMAD7 is associated with CHD, we conducted a case-control study in the Han Chinese population. Exon1 and exon4 of SMAD7, which encode the functional MH1 and MH2 domains, were directly sequenced in 1,201 sporadic CHD patients and 1,116 control individuals. A total of 18 sequence variations were identified. Two common variants rs3809922 and rs3809923 are located at exon4 of SMAD7, and were found in strong linkage disequilibrium with each other (r (2) = 0.93). We analyzed the association of these two loci with CHD in 3 independent subgroup case-control studies, and found that in some subgroups, rs3809922 and rs3809923 were significantly associated with CHD through genetic model analysis. In the combined data set, TT genotype in rs3809922 significantly increased the risk of CHD compared with CC and CT, while GG genotype in rs3809923 significantly increased the risk of CHD compared with CC and CG, particularly in the recessive model. In addition, haplotype analyses showed that haplotype TG significantly increased the risk of CHD (P = 6.9×10(-6)); this finding supports the results from the analyses based on single locus. According to data from the 1000 Genomes Project, the frequencies of the two risk alleles varied greatly between populations worldwide, which indicate the identified associations might have a population difference. To our knowledge, this is the first report that genetic variants in SMAD7 influence susceptibility to CHD risk.
    PLoS ONE 01/2013; 8(9):e72423. · 3.53 Impact Factor
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    ABSTRACT: In this work, poly(amide‐amidic acid) (PAA) was used to modify tetraglycidyl 4,4′‐diaminodiphenylmethane (TGDDM)/4,4′‐diaminodiphenylsulfone (DDS) system. Results of non‐isothermal differential scanning calorimetry analysis indicated that PAA played a role of catalyst during the process of the curing reaction. The curing mechanism was studied by Fourier transform infrared spectroscopy, showing that the PAA acted as a co‐curing agent in the system. The glass transition temperature decreased firstly and then increased with the increase of the PAA content. PAA equally rendered TGDDM more fire resistant with higher char yield. On examining the fracture surface morphology using scanning electron microscopy, it was observed that there was no obvious phase separation when the content of PAA was less than 20 phr (per hundred weight of TGDDM/DDS resin), however, phase separation was observed when the content of PAA was 25 and 30 phr. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
    Journal of Applied Polymer Science 01/2013; 128(3). · 1.40 Impact Factor
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    ABSTRACT: Congenital heart disease (CHD) is one of the most prevalent developmental anomalies and the leading cause of noninfectious morbidity and mortality in newborns. Despite its prevalence and clinical significance, the etiology of CHD remains largely unknown. GATA4 is a highly conserved transcription factor that regulates a variety of physiological processes and has been extensively studied, particularly on its role in heart development. With the combination of TBX5 and MEF2C, GATA4 can reprogram postnatal fibroblasts into functional cardiomyocytes directly. In the past decade, a variety of GATA4 mutations were identified and these findings originally came from familial CHD pedigree studies. Given that familial and sporadic CHD cases allegedly share a basic genetic basis, we explore the GATA4 mutations in different types of CHD. In this study, via direct sequencing of the GATA4 coding region and exon-intron boundaries in 384 sporadic Chinese CHD patients, we identified 12 heterozygous non-synonymous mutations, among which 8 mutations were only found in CHD patients when compared with 957 controls. Six of these non-synonymous mutations have not been previously reported. Subsequent functional analyses revealed that the transcriptional activity, subcellular localization and DNA binding affinity of some mutant GATA4 proteins were significantly altered. Our results expand the spectrum of GATA4 mutations linked to cardiac defects. Together with the newly reported mutations, approximately 110 non-synonymous mutations have currently been identified in GATA4. Our future analysis will explore why the evolutionarily conserved GATA4 appears to be hypermutable.
    PLoS ONE 01/2013; 8(4):e62138. · 3.53 Impact Factor
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    ABSTRACT: A series of composites with Twaron fabric as reinforcement and PTFE as matrix were fabricated with various contents of PTFE, viz. 30, 40, 50, 60 and 70 vol%. The Rockwell hardness and tensile strength of the composites were tested according to the corresponding standards. The composites were also evaluated for their tribological behaviors on an MPX-2000A friction and wear tester. The worn surface and wear debris of the composites were observed by scanning electron microscopy (SEM) and the mechanism is discussed. The PTFE content in the composites had a great influence on both the mechanical and tribological properties. The composite with 40 vol% PTFE provided the proper wetting of the fibers and the best load transfer efficency and, hence, showed the best mechanical properties and tribological behaviors.
    Journal of Macromolecular Science Part B 09/2012; · 0.63 Impact Factor
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    ABSTRACT: AbstractA novel curing agent, poly (amide‐amidic acid) (PAA), was used to cure tetraglycidyl 4,4′‐diaminodiphenylmethane (TGDDM). The initial cure and exothermic peak temperatures increased with increase in PAA content. The mechanism for the cure of TGDDM/PAA was proposed which involved, besides TGDDM cure, PAA imidization in the system. Examination of the morphology of the fractured surface using scanning electron microscopy showed that curing with PAA improved more the fracture toughness as compared to the conventional 4,4′‐diaminodiphenylsulfone (DDS), and rendered TGDDM more fire resistant with higher char yield. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
    Journal of Applied Polymer Science 08/2012; 125(4). · 1.40 Impact Factor
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    ABSTRACT: The chemokine receptors and ligand CCR5, CXCR4 and SDF-1 play important roles in the entry of HIV-1 into host cells. Genetic polymorphisms such as CCR5-Δ32 and SDF-1 3'A have been reported to be associated with HIV-1 susceptibility and the progression of AIDS. Considering the remarkable difference in CCR5-Δ32 allele frequency among worldwide populations, we aimed to survey the genetic variations in CCR5, CXCR4 and SDF-1 in different Chinese populations. The open reading frames and regulatory regions of CCR5, CXCR4 and SDF-1 were sequenced in 141 Chinese individuals from three ethnic groups: Han, Mongol and Uyghur. Ninety-six variants were identified, 41 of which were newly identified (NI) in Chinese populations. A novel non-synonymous variant c.459 C>T (Trp153Cys) within CCR5 was identified in one Han individual. Of NI variants, 11 were common polymorphisms with a minor allele frequency (MAF) >5%. The polymorphism CCR5-Δ32 was found in three Uyghur individuals but was absent in Han and Mongol groups. The linkage disequilibrium (LD) analysis of CCR5 and SDF-1 and frequency of CCR5 haplotypes showed considerable divergence among three ethnic groups. Our results show the great genetic heterogeneity within CCR5, CXCR4 and SDF-1 in Chinese ethnic populations.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 07/2012; 12(5):1072-8. · 3.22 Impact Factor
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    ABSTRACT: Carbon fabric reinforced polytetrafluoroethylene (PTFE) composites with different PTFE content, viz. 30, 40, 50, 60, and 70 vol%, were fabricated by a dispersion impregnation technique followed by a hot-press process. The composites were evaluated for their mechanical and tribological properties. The tribological tests were conducted on a friction and wear tester with a ring-on-block arrangement. The mechanical properties were also tested and their relationship with tribological properties was analyzed. The worn surface and wear debris were analyzed by a scanning electron microscope (SEM) to study the wear mechanism. It was found that the resin content had a great influence on both the mechanical properties and the tribological properties, and the tribological properties were correlated with the mechanical properties. The composite with 50 vol% PTFE showed promising tribological behaviors under the selected test conditions.
    Journal of Macromolecular Science. 04/2012; Part B(Vol. 51):786-797.
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    ABSTRACT: Soluble guanylate cyclase (sGC) mediates NO signaling for a wide range of physiological effects in the cardiovascular system and the central nervous system. The α1β1 isoform is ubiquitously distributed in cytosolic fractions of tissues, whereas α2β1 is mainly found in the brain. The major occurrence and the unique characteristic of human sGC α2β1 indicate a special role in the mediation of neuronal communication. We have efficiently purified and characterized the recombinant heme-binding domain of the human sGC α2 subunit (hsGC α2(H)) and heterodimeric α2β1 (hsGC β1(H)-α2(H)) by UV-vis spectroscopy, circular dichrosim spectroscopy, EPR spectroscopy, and homology modeling. The heme dissociation and related NO/CO binding/dissociation of both hsGC α2(H) and hsGC β1(H)-α2(H) were investigated. The two truncated proteins interact with heme noncovalently. The CO binding affinity of hsGC α2(H) is threefold greater than that of human sGC α1(H), whereas the dissociation constant k (1) for dissociation of NO from hsGC α2(H) is sevenfold larger than that for dissociation of NO from hsGC α1(H), although k (2) is almost identical. The results indicate that in comparison with the α1β1 isoform, the brain α2β1 isoform exhibits a distinctly different CO/NO affinity and binding rate in favor of NO signaling, and this is consistent with its physiological role in the activation and desensitization. Molecular modeling and sequence alignments are consistent with the hypothesis that His105 contributes to the different CO/NO binding properties of different isoforms. This valuable information is helpful to understand the molecular mechanism by which human sGC α2β1 mediates NO/CO signaling.
    European Journal of Biochemistry 03/2012; 17(5):719-30. · 3.42 Impact Factor
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    ABSTRACT: Intellectual disability (ID) is a heterogeneous disorder caused by chromosomal abnormalities, monogenic factors and environmental factors. 22q13 deletion syndrome is a genetic disorder characterized by severe ID. Although the frequency of 22q13 deletions in ID is unclear, it is believed to be largely underestimated. To address this issue, we used Affymetrix Human SNP 6.0 array to detect the 22q13 deletions in 234 Chinese unexplained ID patients and 103 controls. After the Quality Control (QC) test of raw data, 22q13 deletions were found in four out of 230 cases (1.7%), while absent in parents of the cases and 101 controls. A review of genome-wide microarray studies in ID was performed and the frequency of 22q13 deletions from the literatures was 0.24%, much lower than our report. The overlapping region shared by all 4 cases encompasses the gene SHANK3. A heterozygous de novo nonsense mutation Y1015X of SHANK3 was identified in one ID patient. Cortical neurons were prepared from embryonic mice and were transfected with a control plasmid, shank3 wild-type (WT) or mutant plasmids. Overexpression of the Y1015 mutant in neurons significantly affected neurite outgrowth compared with shank3 WT. These findings suggest that 22q13 deletions may be a more frequent cause for Chinese ID patients than previously thought, and the SHANK3 gene is involved in the neurite development.
    PLoS ONE 01/2012; 7(4):e34739. · 3.53 Impact Factor
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    ABSTRACT: Reinforced phenolic resin (PF) was prepared by in situ polymerization of different fractions of carbon nanotubes (CNTs) that had undergone oxidation. The compressive strength and hardness of the material, according to mechanical property testing, was improved by the modified CNTs. The tribological properties of PF composites were investigated by a block-on-ring friction and wear tester. The results indicated that CNTs reinforced PF showed lower friction coefficient and higher wear resistance, compared with pure PF. The morphologies of the worn surfaces, debris, and transfer films were observed by scanning electron microscopy (SEM) and optical microscopy (OM). A continuous and thinner transfer film formed during the friction test of the composites led to the significant improvement of the tribological properties.
    Journal of Macromolecular Science, Part B. 01/2012; 51(6):1148-1158.
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    ABSTRACT: Waardenburg syndrome type II (WS2) is associated with syndromic deafness. A subset of WS2, WS2A, accounting for approximately 15% of patients, is attributed to mutations in the microphthalmia-associated transcription factor (MITF) gene. We examined the genetic basis of WS2 in a large Chinese family. All 9 exons of the MITF gene, the single coding exon (exon 2) of the most common hereditary deafness gene GJB2 and the mitochondrial DNA (mtDNA) 12S rRNA were sequenced. A novel heterozygous mutation c.[742_743delAAinsT;746_747delCA] in exon 8 of the MITF gene co-segregates with WS2 in the family. The MITF mutation results in a premature termination codon and a truncated MITF protein with only 247 of the 419 wild type amino acids. The deaf proband had this MITF gene heterozygous mutation as well as a c.[109G>A]+[235delC] compound heterozygous pathogenic mutation in the GJB2 gene. No pathogenic mutation was found in mtDNA 12S rRNA in this family. Thus, a novel compound heterozygous mutation, c.[742_743delAAinsT;746_747delCA] in MITF exon 8 was the key genetic reason for WS2 in this family, and a digenic effect of MITF and GJB2 genes may contribute to deafness of the proband.
    Journal of Genetics and Genomics 12/2011; 38(12):585-91. · 2.08 Impact Factor
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    ABSTRACT: Reinforced phenol resin (PF) was prepared by in situ polymerization of different fractions of nano polytetrafluoroethylene particles (nano-PTFE) undergone grafting acrylic acid irradiation. The bending strength and hardness of the material, according to mechanical property testing, were improved by the grafted nano-PTFE. The tribological properties of PF composites were investigated by a block-on-ring friction and wear tester. The results indicated that nano-PTFE reinforced PF showed lower friction coefficient and higher wear resistance, compared with pure PF. The morphologies of the worn surfaces, debris and transfer films were observed by a scanning electron microscopy (SEM) and an optical microscopy (OM). A continuous and thinner transfer film formed during the friction test led to the significant improvement on the tribological properties.
    Materials Science and Engineering A 08/2011; 528(22):6878-6886. · 2.41 Impact Factor
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    ABSTRACT: Human soluble guanylate cyclase (sGC), a critical heme-containing enzyme in the NO-signaling pathway of eukaryotes, is an αβ heterodimeric hemoprotein. Upon the binding of NO to the heme, sGC catalyzes the conversion of GTP to cyclic GMP, playing a crucial role in many physiological processes. However, the specific contribution of the α and β subunits of sGC in the intact heme binding remained intangible. The recombinant human sGC α1 subunit has been expressed in Escherichia coli and characterized for the first time. The heme binding and related NO/CO binding properties of both the α1 subunit and the β1 subunit were investigated via heme reconstitution, UV-vis spectroscopy, EPR spectroscopy, stopped-flow kinetics, and homology modeling. These results indicated that the α1 subunit of human sGC, lacking the conserved axial ligand, is likely to interact with heme noncovalently. On the basis of the equilibrium and kinetics of CO binding to sGC, one possible CO binding model was proposed. CO binds to human sGCβ195 by simple one-step binding, whereas CO binds to human sGCα259, possibly from both axial positions through a more complex process. The kinetics of NO dissociation from human sGC indicated that the NO dissociation from sGC was complex, with at least two release phases, and human sGCα259 has a smaller k (1) but a larger k (2). Additionally, the role of the cavity of the α1 subunit of human sGC was explored, and the results indicate that the cavity likely accommodates heme. These results are beneficial for understanding the overall structure of the heme binding site of the human sGC and the NO/CO signaling mechanism.
    European Journal of Biochemistry 07/2011; 16(8):1227-39. · 3.42 Impact Factor
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    ABSTRACT: The tribological properties of polyoxymethylene (POM) modified by nano-polytetrafluorethylene (nano-PTFE) were investigated by a block-on-ring wear tester. For comparison, modified POM with micro-polytetrafluoroethylene (micro-PTFE) was also studied. The modified POM with a much lower concentration of nano-PTFE showed the similar tribological properties compared with POM modified by micro-PTFE. The friction coefficient decreased with the increase of nano-PTFE, while the wear rate showed the lowest value when the concentration of nano-PTFE was 2%. Scanning electron microscope (SEM) micrographs revealed that transfer films played an important role in the friction process. The transfer films decreased and stabilized the friction coefficient. Comparing to POM/2%nano-PTFE, when the concentration of nano-PTFE reached 4%, the mechanical properties decreased significantly, possibly due to poor dispersion of nano-PTFE.
    Journal of Macromolecular Science. 07/2011; Part B(Vol. 50):1235-1248.
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    ABSTRACT: 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA)-based copolyimides were synthesized and the tribological properties of the copolyimides with different heat histories were studied at different temperatures. Fluoride-containing polyimide (PI) showed better thermal stability, decreased friction coefficients, and postponed the consequence of friction variation, which depended on temperature, than nonfluorinated PI. Thermal treatments seemed to increase the friction coefficients of copolyimides, and reduced the tensile strengths of the materials. The effects of applied load (P) and sliding speed (V) on tribological behaviors of thermally treated copolyimides were also examined and the variations of friction coefficient depending on PV values were investigated for clear understanding of its relationship between PV value and friction coefficient with different thermal treating time. Distortions of net structures of the chains and molecular motion contributed to variations of tribological properties of thermal treated copolyimides.
    Journal of Macromolecular Science Part B 05/2011; Part B(Vol. 50):860-870. · 0.63 Impact Factor
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    ABSTRACT: Although recent genome-wide association studies have been conducted to reveal the relation between variations in the α5 nicotinic receptor subunit and lung cancer in European and American populations, to the authors' knowledge, no definite information on the role of nicotine acetylcholine receptor subunit α5 (CHRNA5) in lung cancer risk has been obtained in a Chinese population. To test this possible association, a case-control study was conducted in 505 patients with lung cancer (cases) and a control group of 498 cancer-free individuals. Participants were screened for variations in the CHRNA5 promoter region by sequencing, and 2 common polymorphisms were selected at -1640 (reference single nucleotide polymorphism identifier rs3829787 cytosine to thymine [C→T]) and at -62 (rs3841324 insertion→deletion [ins→del]) from the transcription start site of the CHRNA5 gene. Haplotype analysis revealed that the 2 least frequent haplotypes (T/ins and C/del) were statistically protective against lung cancer (P = .0002 and P = .0094, respectively). Unexpectedly, the luciferase results indicated that these 2 protective haplotype constructs had the extremely opposite promoter activity in various cells: the T/ins haplotype had the highest activity and the C/del haplotype had the lowest activity. Surface plasmon resonance demonstrated that both minor alleles (T and del) decreased DNA binding affinity to nuclear extracts, which the authors presumed was responsible for the disparity in promoter activity. The current results indicated that the CHRNA5 gene with under-activated or over-activated promoter activity may be protective against lung cancer. These results indicated a new associated risk pattern between CHRNA5 promoter activity and susceptibility to lung cancer that implies a complex role of the CHRNA5 gene in lung cancer. Cancer 2011;. © 2011 American Cancer Society.
    Cancer 03/2011; 117(20):4714-23. · 5.20 Impact Factor
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    ABSTRACT: Dentinogenesis imperfecta (DGI) type II is an autosomal dominant disease characterized by a serious disorders in teeth. Mutations of dentin sialophosphoprotein (DSPP) gene were revealed to be the causation of DGI type II (DGI-II). In this study, we identified a novel mutation (NG_011595.1:g.8662T>C, c.135+2T>C) lying in the splice donor site of intron 3 of DSPP gene in a Chinese Han DGI-II pedigree. It was found in all affected subjects but not in unaffected ones or other unrelated healthy controls. The function of the mutant DSPP gene, which was predicted online and subsequently confirmed by in vitro splicing analysis, was the loss of splicing of intron 3, leading to the extended length of DSPP mRNA. For the first time, the functional non-splicing of intron was revealed in a novel DSPP mutation and was considered as the causation of DGI-II. It was also indicated that splicing was of key importance to the function of DSPP and this splice donor site might be a sensitive mutation hot spot. Our findings combined with other reports would facilitate the genetic diagnosis of DGI-II, shed light on its gene therapy and help to finally conquer human diseases.
    PLoS ONE 01/2011; 6(11):e27982. · 3.53 Impact Factor

Publication Stats

211 Citations
78.63 Total Impact Points

Institutions

  • 2009–2012
    • Fudan University
      • • Institutes of Biomedical Sciences
      • • Department of Chemistry
      • • School of Life Sciences
      Shanghai, Shanghai Shi, China
  • 2009–2010
    • Shanghai Institutes for Biological Sciences
      Shanghai, Shanghai Shi, China