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Evaluated the Value of Hb A for Screening Newborn Beta Thalassemia

Evaluated the Value of Hb A for Screening Newborn Beta Thala...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Huang Peng Chen Qiuli He Sheng Chen Biyan Lin Li Wei Yuan Xiong Fu Xu Xiang-min Medical Genetics departments Southern medical universityGuangzhou Central Laboratory of Genetic and Metabolism MCH Hospital of Guangxi Autonomous region

Objective To validate the relationship of Hb A composition in newborn peripheral blood and age/g estation-week/weight. To evaluate the value of Hb A for newborn beta thalassemia screening. Method Retrospective analysis 23,586 cases newborn peripheral blood thalassemia screening, t he hemoglobin was detected by capillary electrophoresis;selected 766 cases with Hb A percentag e composition less than 12.0, and genomic DNA was extracted for detecting beta gene mutations by conventional PCR-RDB. 222 cases with abnormal Hb A but without any mutation were further d etected by Sanger-sequencing. Analyzing the relationship of Hb A and beta gene mutation by SP SS. Result There are 4,372 cases high-risk thalassemia of all the 23,586 cases screening, of which, 2,631 cases alpha thalassemia(Hb-Bart‘s or Hb-CS) and 1,741 cases beta thalassemia(Hb A<9.4 or Hb E), the median value of Hb A in population is 17.66. When neonatal age was little than 15 days, there‘s no distinction in Hb A composition(P>0.05);but when older than 15 days, Hb A raise following the age growing, and Hb A composition rise to 85% when 4 month old;moreover, Hb A a nd gestation weeks are positive correlated;whereas, there are no significant relationship between birth weight and Hb A. When Hb A composition threshold defined at 10.5, beta thalassemia scree ning specificity up to 95% with 20.8% of sensitivity, when defined at 11.2, the specificity and sensi tivity is 98% and 14.7%, respectively. Conclusion Comprehensive analysis screening data, we proposed Hb A=10.5 as threshold for ne wborn beta thalassemia screening. To guarantee the screening results, we suggested that neonat al should be less than 15 days old, in addition, gestation week should be consideration.

关键词： Evaluated the Value of Hb A for Screening Newborn Beta Thalassemia

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A novel FOXL2 mutation was identified in one family with both types of blepharophimosis-ptosis-epicanthus inversus syndrome

A novel FOXL2 mutation was identified in one family with bot...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： yang lin xing yiqiao li tuo Department of Ophthalmology Renmin Hospital of Wuhan University Department of Ophthalmology The Central Hospital of Enshi Autonomous Prefecture

Objective Purpose: Blepharophimosis-ptosis-epicanthus inversus syndrome（BPES） is a rare autosomal dominant disease, which has been divided into two types according to whether it has premature ovarian failure. Mutations in FOXL2 has been identified in most patients with *** study aims to identify the causative mutation in FOXL2 in a Chinese family with both types of BPES. Method Methods: Clinical data and genomic DNA were collected from a Chinese family with BPES. All coding exons and adjacent regions of FOXL2 were screened in one affected member to detect causative mutation by Sanger sequencing. The detected mutation would be further screened in available family members as well as 100 normal control chromosomes. Result Results: Seven members of the family were recruited in this study, including four affected and three unaffected. The patient II: 5 showed typical features of type II BPES characterized by a narrowed horizontal palpehral aperture, ptosis, epicanthus inversus and telecanthus without premature ovarian failure（POF）, whereas all her three daughters（III:1, III:2, III:3） were diagnosed with type I BPES, in which a complex eyelid malformation is accompanied with POF. A novel heterozygous mutation in FOXL2（c.84460 dup17, ***291 Argfs*71） was found in the four affected members and was absent in the other three unaffected members as well as 100 control chromosomes. Conclusion Conclusions: A novel duplicate mutation（c.84460 dup17, ***291 Argfs*71） in FOXL2 was identified in a Chinese family with both types of BPES. Our findings expand the mutation spectrum of the FOXL2 gene and confirmed the intra-family phenotypic heterogeneity of BPES.

关键词： A novel FOXL2 mutation was identified in one family with both types of blepharophimosis-ptosis-epicanthus inversus syndrome

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De novo mutation of KAT6B gene in a patient with short stature

De novo mutation of KAT6B gene in a patient with short statu...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Li Guoqiang Li Niu Li Juan Ding Yu YU Tingting Wang Xiumin Wang Jian Institute of Pediatric Translational Medicine Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine Departments of Medical Genetics Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine Departments of Endocrinology Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine Departments of Laboratory Medicine Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine

Objective Short stature is defined as a height more than two standard deviations(SD) below the mean height for a given age, gender, and population. Short stature in childhood is a common reason for referral to pediatric endocrine clinics. It can be observed under a wide variety of conditions, and over 700 genes are known to be associated with it. Mutations in the KAT6 B gene are responsible for Say-Barber-Biesecker-Young-Simpson syndrome(SBBYSS) and genitopatellar syndrome(GPS), which share some clinical features, including developmental delay and intellectual disability, congenital heart defects, and genital and patellar anomalies, though short stature is not a common feature of *** aim of this research is to explore the genetic basis of the *** Targeted next-generation sequencing was performed on a Chinese pediatric patient who mainly showed short stature but no other obvious symptoms. Sanger sequencing was used to verify of the mutation of KAT6 B gene and evaluate the parents of the patient. Result DNA sequencing revealed a de novo mutation in exon 14 of KAT6 B gene at position c.2636 T>A(***879 X), and the novel nonsense mutation was interpreted to be pathogenic according to the standards and guidelines for the interpretation of sequence variants from American College of Medical Genetics and Genomics(ACMGG). Conclusion To the best of our knowledge, this is the first report of KAT6 B gene mutation in any Chinese individual.

关键词： De novo mutation of KAT6B gene in a patient with short stature

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Bioinformatics analysis of gene expression profiles of dermatomyositis

Bioinformatics analysis of gene expression profiles of derma...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Chen Liangyuan Department of Medical Genetics Fuzhou General Hospital

Objective Dermatomyositis(DM) is a type of autoimmune inflammatory myopathy, which primaril y affects the skin and muscle. The underlying mechanisms of DM remain poorly understood. The present study aimed to explore gene expression profile alterations, investigate the underlying me chanisms, and identify novel targets for DM. Method The GSE48280 dataset, which includes data from five DM and five normal muscle tissue samples, was obtained from the Gene Expression Omnibus. Firstly, differentially expressed gene s(DEGs) were screened by limma package in R. Subsequently, functional and pathway enrichme nt analyses were performed using Clue GO from Cytoscape. Finally, protein?protein interaction(P PI) networks were constructed using STRING and Cytoscape, in order to identify hub genes. Result As a result, 180 upregulated and 21 downregulated genes were identified in the DM samp les. The Gene Ontology enrichment analysis revealed that the type I interferon(IFN) signaling pat hway was the most significantly enriched term within the DEGs. The Kyoto Encyclopedia of Gene s and Genomes pathway analysis identified 27 significant pathways, the majority of which can be divided into the infectious diseases and immune system categories. Following construction of PPI networks, 24 hub genes were selected, all of which were associated with the type I IFN signaling pathway in DM. Conclusion The findings of the present study indicated that type I IFNs may have a central role i n the induction of DM. In addition, other DEGs, including chemokine(C?C motif) ligand 5, C?X?C motif chemokine 10, Toll?like receptor 3, DEXD/H?Box helicase 58, interferon induced with helic ase C domain 1, interferon?stimulated gene 15 and MX dynamin?like GTPase 1, may be potentia l targets for DM diagnosis and treatment.

关键词： Cytoscape Bioinformatics analysis of gene expression profiles of dermatomyositis

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Loss of TRPS1 stimulates Epithelial-Mesenchymal Transition and metastasis through FOXA1 repression

Loss of TRPS1 stimulates Epithelial-Mesenchymal Transition a...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Yan Guang-Rong Huang Jin-Zhou Chen Min Biomedicine Research Center The Third Affiliated Hospital of Guangzhou Medicinal University Key Laboratory for Major Obstetric Diseases of Guangdong Province Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes

Objective The tricho-rhino-phalangeal syndrome 1(TRPS1) gene, which was initially found to be associated with tricho-rhino-phalangeal syndrome, is critical for the development and differentiation of bone, hair follicles and kidney. However, its role in cancer progression is largely unknown. Method The functions of TRPS1 were analyzed by cellular biological assays in vitro and in vivo. Result We here demonstrated that down-regulation of TRPS1 correlated with distant metastasis, tumor recurrence and survival rate in cancer patients. TRPS1 was frequently down-regulated in high-metastatic breast, colon and nasopharyngeal cancers, and silencing of TRPS1 stimulated epithelial-mesenchymal transition(EMT), migration and invasion in vitro and metastasis in vivo, while TRPS1 over-expression exhibited the opposite effects. Using quantitative proteomics, the negative EMT regulator FOXA1 was shown to be down-regulated by TRPS1 knockdown. Ectopic expression of FOXA1 blocked the enhancement of EMT, migration and invasion induced by TRPS1 silencing. Mechanistically, TRPS1, acting as a transcription activator, directly induced FOXA1 transcription by binding to the FOXA1 promoter. We further showed that down-regulation of TRPS1 was induced by mi R-373 binding to the 3‘UTR of TRPS1. TRPS1, but not TRPS1-3‘UTR, over-expression blocked the enhancement of migration and invasion induced by mi R-373. Conclusion Loss of TRPS1 by mi R-373, acting as a transcriptional activator, promotes EMT and metastasis by repressing FOXA1 transcription, expanding upon its previously reported role as a transcription repressor.

关键词： Loss of TRPS1 stimulates Epithelial-Mesenchymal Transition and metastasis through FOXA1 repression

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The carrier rate and mutation spectrum of genes associated with hearing loss in South China hearing female population of childbearing age

The carrier rate and mutation spectrum of genes associated w...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Liu Chang Zhang Yan Wu Jing Ding Hongke Mai Mingqin Zeng Yukun Liu Ling Yin Aihua Medical Genetic Center Guangdong Women and Children Hospital Maternal and Children Metabolic-Genetic Key Laboratory Guangdong Women and Children Hospital

Objective Considering the fact that hearing loss occurs in 1 to 3 of 1,000 live births and approxim ately 90 to 95 percent of them are born into hearing families, it is of importance and necessity to g et better understanding about the carrier rate and mutation spectrum of genes associated with he aring impairment in the general population. Method 32,497 unrelated women of childbearing age with normal hearing and without family hist ory of hearing loss were tested with allele-specific PCR-based universal array. Further genetic tes ts were provided to the spouses of the screened carriers. For those couples at risk, multiple choic es were provided, including prenatal diagnosis. Result Among the 32,497 normal hearing participants, 1,181 subjects carried pathogenic mutatio ns included in the screening chip, which made the carrier rate 3.63%. Of the 1,181 screened carri ers, 1,117 harbored heterozygous mutated genes associated with autosomal recessive hearing loss, and 735 spouses took further genetic tests. 44 out of the 47 couples harbored deafness-causi ng mutations in the same gene received prenatal diagnosis. Conclusion Given that nearly 90 to 95 percent of deaf and hard-of-hearing babies are born into h earing families, better understanding about the carrier rate and mutation spectrum of genes assoc iated with hearing impairment in the female population of childbearing age may be of importance i n carrier screening and genetic counseling.

关键词： The carrier rate and mutation spectrum of genes associated with hearing loss in South China hearing female population of childbearing age

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GRIN2A polymorphism rs1448258 associated with schizophrenia in Chinese Han population

GRIN2A polymorphism rs1448258 associated with schizophrenia ...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Hu jiaxin Bio-X Institutes Shanghai Jiaotong university

Objective Schizophrenia is a polygenetic and clinically heterogeneous disorder with early mortalit y and high heritability. Some studies indicated the dysfunction of neurotransmission mediated by t he downregulated expression of N-methyl-D-aspartic acid receptors(NMDARs) were manifested i n schizophrenic patients. In our study, we employed some statistical approaches to verify whethe r the single nucleotide polymorphisms(SNPs) in RIN2 A underlying an important role in the patho genesis of schizophrenia. Method We recruited 1616 unassociated Han Chinese participants, including 752 schizophrenic patients and 846 normal subjects. Each patient was diagnosed based on DSM-IV(Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria. We genotyped three SNPs of GRI N2 A in 752 schizophrenic patients and 846 normal controls. Genotyping of SNPs was conducted through a matrix-assisted laser desorption/ionization time-of-flight(MALDI-TOF) mass spectromet er using the Mass ARRAY? Analyzer 4 platform(Sequenom, CA, USA). Finally, we employed so me computer tools to conduct the statistic analyisis. Result Consequently, our three SNPs all meet Handy-Weinberg equilibrium. In terms of significa nce of this polymorphism, it showed a positive association with schizophrenia before correction b oth in the allele and genotype distribution(P = 0.02584 and P = 0.02340 respectively). The result of logistic regression analysis in R showed the C/C allele was significantly associated with schizo phrenia in the codominant model(P=0.0231). Result of stratification model showed that rs1448258 remained to be positively associated with schizophrenia in the female group(P=0.01813) but no t the male group. Conclusion Our study is the first time that rs1448258, the SNP of GRIN2 A has been identified, in Chinese Han population, to be associated with the schizophrenia. Our linkage disequilibrium anal ysis suggested these three SNPs formed a block and associated with schizophrenia in

关键词： GRIN2A polymorphism rs1448258 associated with schizophrenia in Chinese Han population

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Human Oocyte Maturation Arrest Caused by A Novel Missense Mutation in TUBB8

Human Oocyte Maturation Arrest Caused by A Novel Missense Mu...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Li Haibo Xiang Jingjing Wang Wei Qian Chunfeng Li Hong Center for Reproduction and Genetics The affiliated Suzhou Hospital of Nanjing Medical University Center for Reproduction and Genetics Suzhou Municipal Hospital

Objective To investigated the mutations of TUBB8 gene in a patient with oocyte maturation arres t at metaphase I. Method Peripheral blood was collected from the patient, her elder sister and their mother after giv ing informed consent. All four exons and intron-exon boundaries of the TUBB8 gene were amplifi ed by polymerase chain reaction（PCR） using Faststart Taq DNA polymerase. The amplified DNA fragments were purified and sequenced in both directions using ABI 3130 Genetic Analyzer. The resulting sequences were compared with the reference sequence of TUBB8（NM77987.2） in th e NCBI database. Result Sequencing analysis revealed a heterozygous mutation c.760 G>T in TUBB8 gene in two affected sisters with persistent infertility, which was not detected in their *** to a lack of g enetic information regarding their father, the heterozygous mutation was inherited with an unknow n pattern. The mutation c.760 G>T found within exon 4 TUBB8 gene of is a novel heterozygous mi ssense mutation, which converts a highly conserved alanine residue to a serine in TUBB8 protein（p.A254 S）. This mutation is not found in db SNP（http://***/SNP/） or in the 1000 Genomes Project database（http://www.1000 ***/）. In addition, the alanine residue is e volutionarily conserved among primate *** mutation indicated a strong pathogenic proba bility by bioinformatics tools for functional prediction with Poly Phen-2（***/p ph2） and Mutation Taster（***）. Conclusion Our finding expanded the known mutation spectrum of TUBB8 gene and confirmed t he key role of TUBB8 in meiotic spindle assembly and human oocyte maturation.

关键词： Human Oocyte Maturation Arrest Caused by A Novel Missense Mutation in TUBB8

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Association study of GRIK4 polymorphisms and major depressive disorder in the Han Chinese population

Association study of GRIK4 polymorphisms and major depressiv...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Ren Decheng Bio-X institute Shanghai Jiaotong university

Objective Major depressive disorder(MDD) is a common and complex mental disorder characte rized by depression. Recent studies found that glutamate ionotropic receptor kainate type subunit 4(GRIK4) is associated with the MDD and the gene GRIK4, therefore, may be a candidate gene f or many mental disorder especially MDD. In this study, we investigated whether single nucleotide polymorphisms(SNPs) in GRIK4 were associated with *** In the case-control study, we recruited 568 unrelated major depressive disorder patients and 846 healthy controls. All patients were diagnosed on the basis of DSM-IV criteria. We had ge notyped five SNPs using the matrix-assisted laser desorption/ionization time of flight(MALDI-TOF) mass spectrometer on Mass ARRAY? Analyzer 4 platform(Sequenom, San Diego, CA). Design of probes and primers was by using the Mydequenom online software--the accompanying Assay Design Suite v2.0. Several softwares was conducted to do the statistic analysis. Result The results showed that rs56275759 demonstrated statistically significant difference betw een MDD patients and control subjects both in allelic frequencies(P value = 0.011449) and genot ypic frequencies(P value = 0.029024). Rs4582985 was deviated from the Hard-Weinberg equilibr ium so we excluded it from further analysis. Strong LD was found among rs4582985, rs6589847 and rs56275759, and the significant association between this block and MDD was found. Conclusion In summary, our results indicated that rs56275759 in GRIK4 might be correlated with MDD in the Han Chinese population. MDD, a severe and complex psychiatric disorder, is affecte d by many elements such as genetic, psychological and environmental factors. The study may pr ovide a reference for future studies of MDD. The SNPs we studied may be used as a marker for p redicting the MDD in the disease diagnose.

关键词： MDD Association study of GRIK4 polymorphisms and major depressive disorder in the Han Chinese population

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EFFECT OF PH ON THE DEVELOPMENT OF EMBRYOS IN VITRO UNDER THE INFLUENCE OF TEMPERATURE, OSMOLARITY AND OXYGEN.

EFFECT OF PH ON THE DEVELOPMENT OF EMBRYOS IN VITRO UNDER TH...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： WANG WEI HENAN PROVENCIAL PEOPLES HOSPITAL

Objective It is crucial for IVF laboratories to reduce the stress upon embryos for optimizing the in vitro culture environment. The term of p H is one of the parameters influencing the embryo development and is complex to define what the optimal range is. The primary objectives of this study was to explore the effect of differing p H conditions on embryos developments under the other three variables including temperature, oxygen tension and osmolarity. Moreover, this plan also aims to examine the interactions of these four environmental variables. Method In this experimental study, multifactorial design was worked out including 30 different treatment combinations of 4 parameters;temperature, osmolarity, p H and oxygen. There were three different p H, temperature, osmolarity and two different oxygen tensions involved in the plan. The treatment combinations are randomized by Latin square design and separated into three groups to avoid operator variability. The original p H of the Global? medium was used as control treatment condition(p H2 Osm2) and then also used to set up lower and higher conditions. Culture medium preparation and modification were carried out every week. For osmolarity modification, S3 solution and sterile water were used to set higher and lower osmolarity. The source of mouse embryos used in this study was commercialized to avoid potential staring variability. Minc TM incubator was switched between different temperatures and oxygen tensions to culture embryos from different treatment conditions with constant carbon dioxide concentration. The developmental stages of embryos were recorded with blastocysts were qualified on day 5. Blastocysts were stained and visualized under Eclipse 90 i(Nikon) at the end of each experimental week. The experimental plan was completed by a group of 4 operators within 6 weeks. Result On day 5, the number of blastocysts was recorded and all of them were evaluated using the scoring system described by Gardner‘s and Schoo

关键词： EFFECT OF PH ON THE DEVELOPMENT OF EMBRYOS IN VITRO UNDER THE INFLUENCE OF TEMPERATURE OSMOLARITY AND OXYGEN

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