Publications (29)53.96 Total impact
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Article: Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing.
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ABSTRACT: OBJECTIVE: To determine whether non-invasive prenatal testing by maternal plasma DNA sequencing can uncover all fetal chromosome aneuploidies in one simple sequencing event. METHODS: Plasma samples from 435 pregnant women at high risk for Down syndrome were collected prior to amniocentesis in three hospitals in China between March 2009 and June 2011. We sequenced the plasma DNA extracted from these samples at low coverage. We discovered that the genome representation of each of the 24 chromosomes obeyed a linear relationship to its GC content. Applying this relationship, we analysed the copy number of each of the 24 chromosomes. Full fetal karyotyping was compared with maternal plasma DNA sequencing results. RESULTS: Among the 435 samples, 412 samples (94.7%) have full karyotyping and sequencing results. Sixty-seven samples containing a fetal chromosome aneuploidy, including trisomy 21, trisomy 18, trisomy 13, trisomy 9, monosomy X or others, can be accurately identified with a detection sensitivity of 100% and a detection specificity of 99.71%. Normalization of the chromosome representation values against chromosomal guanine/cytosine base content is the key issue to ensure the accuracy. CONCLUSIONS: Our results indicate that non-invasive detection of fetal chromosome aneuploidies for all 24 chromosomes in one single sequencing event is feasible. © 2013 John Wiley & Sons, Ltd.Prenatal Diagnosis 01/2013; · 2.11 Impact Factor -
Article: [Analysis of four fetuses with de novo chromosomal rearrangments using single nucleotide polymorphism microarray chips].
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ABSTRACT: To assess the value of single nucleotide polymophism (SNP) microarray for delineation of de novo chromosomal rearrangements detected upon prenatal diagnosis. SNP microarray analysis was carried out for 4 fetuses with de novo sSMCs or balanced reciprocal translocations. Genomic DNA was extracted from cord blood samples, and amplified, tagged and hybridized following the manufacturer's protocol. Data were collected and analyzed. No pathogenic CNVs were detected in fetus A, whose sSMCs was verified to be heterochromatin. Fetus B, who had a de novo mosaic sSMCs, was found to have a 9 Mb duplication in 4p12-q13 which is associated with speech delay and mental retardation. No pathogenic CNVs were detected in fetus C who has 2 translocation chromosomes inherited from its mother and 2 chromosomes derived from a de novo translocation. Fetus D, who had a de novo "balanced" reciprocal translocation, was found to have a 25 Mb duplication in 1q25 and a 17 Mb deletion in 9p22. Cases A and C had normal physical and mental evaluation after birth. For its ability to detect cryptic imbalance in de novo sSMCs or balanced reciprocal translocations, SNP-array has provided a powerful aid to conventional karyotype analysis during prenatal diagnosis.Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 12/2012; 29(6):658-61. -
Article: Clinical reasoning: a young man with reversible paralysis, cerebral white matter lesions, and peripheral neuropathy.
Neurology 08/2012; 79(8):e70-2. · 8.31 Impact Factor -
Article: Mutation analysis in chinese patients with cornelia de lange syndrome.
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ABSTRACT: Aims: Cornelia de Lange syndrome (CdLS) is a dominant multisystem developmental disorder and related to mutations of the NIPBL, SMC1A, and SMC3 genes. So far, there has been no report of a mutation analysis in Chinese patients with CdLS, while 12 cases have been clinically described. In the present study, we tried to search for pathogenic mutations of the NIPBL, SMC1A, and SMC3 genes in four patients with CdLS from four unrelated Chinese families. Results: The mutational analysis of the NIPBL, SMC1A, and SMC3 genes by direct sequencing revealed a heterozygous splice-site mutation c.4321G>T(p.V1441L) at exon 20 of NIPBL in proband 2 and a novel heterozygous splice-site mutation c.6589+5G>C at intron 38 of NIPBL in proband 3, which was showed by reverse transcription polymerase chain reaction to generate both the full-length and an alternatively spliced transcript with an exon 38 deletion. Conclusions: This is the first report of the mutation analysis of NIPBL in China and our findings both expand the mutation spectrum of NIPBL and provide data for further understanding of the diverse and variable effects of NIPBL mutations.Genetic Testing and Molecular Biomarkers 08/2012; 16(9):1130-4. · 1.11 Impact Factor -
Article: Three patients with Wolf-Hirschhorn syndrome carrying a satellited chromosome 4p.
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ABSTRACT: Wolf-Hirschhorn syndrome (WHS) is caused by a deletion involving the 4p16.3 region. Approximately 70% of WHS patients have a de novo isolated deletion and 22% involve unbalanced translocations. However, WHS with unbalanced rearrangements involving the short arm of an acrocentric chromosome are infrequently reported. Cytogenetic and molecular analyses by using standard G-banding, argyrophilic nucleolar organiser region (Ag-NOR) staining, fluorescence in situ hybridization, and single nucleotide polymorphism array for copy number detection were performed in three patients with WHS phenotype from two Chinese families. A heterozygous 2,767,380-bp terminal 4p deletion was detected in patients 1 and 2 and a heterozygous 5,047,291-bp terminal 4p deletion was detected in patient3. Clinical comparisons among our patients and previously reported cases have been reviewed. Two terminal 4p deletions were identified in three WHS patients with a satellited 4p and an attempt was made to refine the genotypic-phenotypic correlations of the deleted regions.Birth Defects Research Part A Clinical and Molecular Teratology 05/2012; 94(7):549-52. · 2.27 Impact Factor -
Article: Expression of reconstructive hFVIII in the hrDNA by using hrDNA targeting vector
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ABSTRACT: Our lab has constructed a new nonviral vector—hrDNA targeting vector(pHrneo). pHrneo is a human derived vector that can target gene into human ribosomal DNA(hrDNA) locus. In this study, we inserted expression cassette of reconstructive hFVIII (hFVIII-BDDAK39) to pHrneo to construct targeting vector: pHrneo-BDDAK39. Through electroporation of pHrneo-BDDAK39 into HT1080 cells, we identified the homologous recombinants by PCR and Southen blotting, and tested the expression of hFVIII-BDDAK39 in the hrDNA locus. The hFVIII-BDDAK39 was successfully targeted into hrDNA locus of HT-1080 by pHrneo-BDDAK39, and the efficiency of site-specific integration was 2.0×10−5. hFVIII-BDDAK39 in hrDNA locus of HT-1080 is found to be able to express efficiently (32±5 ng·106 cells−1 · 24 h−1). Targeting vector pHrneo-BDDAK39 can find use in gene therapy for hemophilia. Keywordshuman derived vector-site-specific integration-targeting expression-reconstructive hFVIIIChinese Science Bulletin 04/2012; 50(19):2187-2192. · 1.32 Impact Factor -
Article: Silica nanoparticle is a possible safe carrier for gene therapy
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ABSTRACT: In order to develop a safe and effective gene therapy carrier, some toxicological and biodynamical experiments were carried out on silica nanoparticles (SiNPs). First we prepared SiNPs with appropriate portions of cyclohexane, deionized water and ethyl silicate, and then transfected the modified SiNPs and GFP plasmid DNA complex into the HT1080 cells to test the effectiveness of transfection for gene therapy. At the same time, we injected the SiNPs into a number of mice through tail vein. Then we made the mice crossed to evaluate the acute, long-term and reproductive toxicity.In vivo distribution analysis and pathological examination were made on both adult mice and their offspring. SiNPs were uniform and had an average diameter of 40 nm, and the modified SiNPs carried exogenous DNA molecules into target cells and the transferred GFP fusion gene was effectively expressed in the cells. The SiNPs injected via tail vein were widely distributed in almost all of tissues, and the injected mice had the ability to reproduce normally. Thein vivo andin vitro results of this study clearly show that SiNPs can be used as a safe and effective carrier for gene transfection and gene therapy. Keywordssilica nanoparticles (SiNPs)-carrier-gene therapy-toxicology-reproductionChinese Science Bulletin 04/2012; 50(20):2323-2327. · 1.32 Impact Factor -
Article: Targeting of the human coagulation factor IX gene at rDNA locus of human embryonic stem cells.
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ABSTRACT: Genetic modification is a prerequisite to realizing the full potential of human embryonic stem cells (hESCs) in human genetic research and regenerative medicine. Unfortunately, the random integration methods that have been the primary techniques used keep creating problems, and the primary alternative method, gene targeting, has been effective in manipulating mouse embryonic stem cells (mESCs) but poorly in hESCs. Human ribosomal DNA (rDNA) repeats are clustered on the short arm of acrocentric chromosomes. They consist of approximately 400 copies of the 45S pre-RNA (rRNA) gene per haploid. In the present study, we targeted a physiological gene, human coagulation factor IX, into the rDNA locus of hESCs via homologous recombination. The relative gene targeting efficiency (>50%) and homologous recombination frequency (>10(-5)) were more than 10-fold higher than those of loci targeted in previous reports. Meanwhile, the targeted clones retained both a normal karyotype and the main characteristics of ES cells. The transgene was found to be stably and ectopically expressed in targeted hESCs. This is the first targeting of a human physiological gene at a defined locus on the hESC genome. Our findings indicate that the rDNA locus may serve as an ideal harbor for transgenes in hESCs.PLoS ONE 01/2012; 7(5):e37071. · 4.09 Impact Factor -
Article: Novel compound heterozygous mutation of MLYCD in a Chinese patient with malonic aciduria.
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ABSTRACT: A 3-year-old Chinese boy presented with prominent clinical features of malonic aciduria, including developmental delay, short stature, brain abnormalities and massive excretion of malonic acid and methylmalonic acid. Molecular characterization by DNA sequencing analysis and multiplex ligation-dependent probe amplification of the MLYCD gene revealed a heterozygous mutation (c.920T>G, p.Leu307Arg) in the patient and his father and a heterozygous deletion comprising exon 1 in the patient and his mother. The missense mutation (c.920T>G) was not found in 100 healthy controls and has not been reported previously. Our findings expand the number of reported cases and add a novel entry to the repertoire of MLYCD mutations.Molecular Genetics and Metabolism 09/2011; 105(1):79-83. · 3.19 Impact Factor -
Article: A patient with apparently reciprocal translocation and cryptic 10p deletion.
American Journal of Medical Genetics Part A 07/2011; 155A(7):1753-5. · 2.39 Impact Factor -
Article: Mutation analysis of the SRY, NR5A1, and DHH genes in six Chinese 46,XY women.
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ABSTRACT: To determine the genetic cause of 46,XY sex reversal in six Chinese women. G-banded karyotyping and mutation analysis of the SRY, NR5A1, and DHH genes using direct sequencing were performed in six Chinese women aged from 15- to 23-year old with poor sexual development and primary amenorrhea. Clinical, endocrinologic, and ultrasonographic evaluation was reported. Three novel mutations, two heterozygous point mutations in SRY, and one heterozygous microdeletion in NR5A1 were found to be causative in three of the patients. This helps pathogenic study and provides new information for genetic counseling of 46,XY sex reversals.The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 03/2011; 24(6):863-6. · 1.36 Impact Factor -
Article: A family with partial duplication/deletion 4p due to a balanced t (4; 15) (p16.2; p11.2) translocation.
American Journal of Medical Genetics Part A 02/2011; 155A(3):656-9. · 2.39 Impact Factor -
Article: A novel GPR143 splicing mutation in a Chinese family with X-linked congenital nystagmus.
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ABSTRACT: The purpose of the current research was to detect the underlying genetic defect in a Chinese family with X-linked congenital nystagmus and perform prenatal genetic diagnosis for their current pregnancy. A common clinical examination and an ophthalmic evaluation were performed on the proband, one carrier, and one unaffected member. Mutation analysis of the G protein-coupled receptor 143 (GPR143) and four-point-one (4.1), ezrin, radixin, moesin (FERM) domain-containing 7 (FRMD7) genes was performed by direct sequencing of PCR-amplified exons in the proband. The detected GPR143 mutation was tested in all available family members and 200 normal controls by direct sequencing. Congenital nystagmus, obvious fundus hypopigmentation, and foveal hypoplasia were observed in the proband but not in the carriers or the unaffected members. A novel splicing mutation c.658+1 g>t not found in 200 unrelated controls was identified and co-segregated with X-linked ocular albinism (XLOA) in this family. The fetus (V:5) was hemizygous for this mutant allele. We identified a novel causative mutation of GPR143 in a five-generation Chinese family with XLOA. This expanded the mutation spectrum of GPR143 and provided data elucidating the diverse and variable effects of GPR143 mutations.Molecular vision 01/2011; 17:715-22. · 2.20 Impact Factor -
Article: A non-viral vector for potential DMD gene therapy study by targeting a minidystrophin-GFP fusion gene into the hrDNA locus.
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ABSTRACT: Gene therapy has emerged as a promising approach for the lethal disorder of Duchenne muscular dystrophy (DMD). Using a novel non-viral delivery system, the human ribosomal DNA (hrDNA) targeting vector, we targeted a minidystrophin-GFP fusion gene into the hrDNA locus of HT1080 cells with a high site-specific integrated efficiency of 10(-5), in which the transgene could express efficiently and continuously. The minidystrophin-GFP fusion protein was easily found to localize on the plasma membrane of HT1080 cells, indicating its possible physiologic performance. Our findings showed that the hrDNA-targeting vector might be highly useful for DMD gene therapy study.Acta Biochimica et Biophysica Sinica 12/2009; 41(12):1053-60. · 1.38 Impact Factor -
Article: [Identification of the small supernumerary marker chromosomes in two patients with Turner syndrome].
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ABSTRACT: To identify the small supernumerary marker chromosomes (sSMC) and guide the genetic counseling and medical treatment in two patients with Turner syndrome. High resolution GTG and C banding, SRY amplification by PCR and fluorescence in situ hybridization (FISH) on metaphase chromosomes were performed to the two patients. The karyotypes of the two patients were 45, X [29]/46,X, +mar[31] and 45,X[71]/46,X, +mar[29] respectively. SRY test indicated SRY-positive for patient 1, whose sSMC was originated from chromosome Y. The karyotype was confirmed as 45,X[29]/46,X,idic(Y)(q10)[31]. ish idic(Y)(q10)(RP11-115H13x2) (SRY+) by FISH. While in patient 2, the sSMC was originated from chromosome X, whose karyotype was determined as 45, X[71]/46,X, r(X)(p11.23q21)[29]. ish r(X) (p11.23q21)(AL591394.11xAC092268.3). Using cytogenetic and molecular cytogenetic analyses, we have identified the sSMCs in two patients with Turner syndrome, which was helpful to the clinical diagnosis and treatment.Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 12/2009; 26(6):659-63. -
Article: [Genetic diagnosis and prenatal diagnosis of Angelman syndrome].
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ABSTRACT: To evaluate the conventional cytogenetic methods in genetic diagnosis and prenatal diagnosis in the family with a proband of Angelman syndrome (AS). High-resolution G-banding karyotyping and fluorescence in situ hybridization (FISH) on metaphase chromosomes were performed. Two AS patients and 1 normal fetus in the family were successfully detected by FISH. Our result demonstrated that patient with type I AS could be detected by combining the techniques of high-resolution G-banding and FISH with clinical observation, which would offer accurate genetic counseling information to the geneticists and provide the prenatal diagnosis for the AS family.Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 10/2009; 26(5):511-3. -
Article: [Rapid detection of the hot spot gene mutations in Chinese patients with nonsyndromic hearing loss by polymerase chain reaction-restrictive fragment length polymorphism].
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ABSTRACT: To develop a rapid genetic diagnosis technique for the patients with hereditary hearing loss by screening hot spots of mutations, namely 235delC of the GJB2 gene, IVS7-2A>G of the SLC26A4 gene, and 1555A>G of mitochondrial 12S rRNA. Multiple PCR amplification of the three fragments covering the expected mutations in GJB2, SLC26A4 and 12S were carried out and the amplified products were analyzed by restriction fragment length polymorphism (RFLP). Eighteen homozygous and 18 heterozygous 235delC, 2 homozygous and 13 heterozygous IVS7-2A>G, and 8 homogeneous 1555A>G were detected in the 200 patients with hearing loss. All the results were confirmed by sequencing. The detection rate of the three mutant alleles was 21.7% (71/400 + 8/200 = 0.217) and the genetic diagnosis rate was 14% [(18+2+8)/200 = 0.14]. It is a convenient, efficient and economical method to screen the hot spots of mutation in the patient with hereditary hearing loss by using PCR-RFLP.Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 10/2009; 26(5):518-20. -
Article: A ZRS duplication causes syndactyly type IV with tibial hypoplasia.
American Journal of Medical Genetics Part A 03/2009; 149A(4):816-8. · 2.39 Impact Factor -
Article: [Mutational screening of the SLC26A4 gene in patients with nonsyndromic hearing loss by denaturing high-performance liquid chromatography].
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ABSTRACT: To study the SLC26A4 gene mutations in patients with nonsyndromic hearing loss (NSHL) and provide the clinical guidance of gene diagnosis. PCR and denaturing high-performance liquid chromatography (DHPLC) were used to screen the 21 exons and their flanking regions of the SLC26A4 gene. Samples with abnormal DHPLC wave patterns were sequenced to identify the variations. Among the 30 unrelated NSHL patients in whom no deafness-causing mutations of the GJB2 gene were identified, 10 types of variations were detected, including 7 known mutations, 2 novel mutations (F572L and D87Y), and 1 known polymorphism (Ivs11+47T>C). The Ivs7-2A>G is the most common type of variation, accounting for 40% of all the mutations. SLC26A4 mutation is a major cause of NSHL, just next to the GJB2 mutations. For NSHL patients without deafness-causing GJB2 mutations, the SLC26A4 mutation rate was 23.3%, and the Ivs7-2A>G was the most common mutation.Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 02/2009; 26(1):21-5. -
Article: [Mutation screening of the dystrophin gene in 14 Chinese Duchenne/Becker muscular dystrophy patients without gross deletions].
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ABSTRACT: To search for the dystrophin gene mutations of Duchenne muscular dystrophy (DMD) patients without gross deletions, in order to offer accurate genetic counseling and prenatal diagnosis for those families. All 79 exons of the dystrophin gene as well as its 5'-UTR and 3'-UTR of 14 Chinese DMD/Becker muscular dystrphy (BMD) patients without detectable gross deletions were screened by denaturing high performance liquid chromatography (DHPLC) and heteroduplex fragments were identified by subsequent sequencing. Seven causative point mutations, including two novel ones, were detected in 7 patients. Fourteen known polymorphisms and 7 unknown intronic variations were also detected. Five mothers of the patients were obligate carriers. DHPLC is an efficient way of identifying point mutations and the female carriers in DMD families.Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 01/2009; 25(6):633-6.
Top co-authors
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Institutions
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2005–2013
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Central South University
- State Key Laboratory of Medical Genetics
Changsha, Hunan, China
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2009–2012
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State Key Laboratory of Medical Genetics of China
Changsha, Hunan, China
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