Objective: To investigate the efficiency of maternal serum triple screening for the genetic abnormality in second-trimester and the morbidity of adverse pregnancy outcome in false positive results of the test. Methods...Objective: To investigate the efficiency of maternal serum triple screening for the genetic abnormality in second-trimester and the morbidity of adverse pregnancy outcome in false positive results of the test. Methods: A total of 4 680 pregnant women with singleton pregnancies assigned in Obs & Gyn Hospital, Fudan University, underwent triple screening test (alpha fetoprotein, AFP; human chorionic gonadotropin, HCG and unconjugated estriol, uE3) by fluorescence enzyme immunoassay between 2003 and 2005. The valid MoM (Multiples of Median) value of mid-trimester serum AFP, uE3, and hCG and risk assessments was provided by Beckman Coulter Co. when applied in the prenatal Down syndrome screening service. The study compares the incidence of chromosomal abnormalities with Down syndrome in screen positive women and compares to the MoM value established in the literature. The risks of having a fetus with congenital abnormalities or of developing obstetric complications in the screen positive women with their matched controls.Results:The MoM values for the triple tests of our study are similar to established values of literature. Only 51.01% women with pregnancies agree to receive screening. Amniocentesis utilization rate was 55.12% in the screen-positive pregnancies. The false positive rate was 6.89% and the median of maternal age of the women was 28.13 (range 19 to 49) years old. Chromosomal abnormalities were identified in 21 pregnancies, including 9 cases of trisomy 21.The detection rate was 77.77%. Pregnancies with positive screening results had a significantly higher risk of adverse outcomes than those with negative results (P< 0.05). Whereas there was no difference in the incidences of fetal congenital appearance or skeleton abnormality. Conclusion: Adjusting MoM values of local unaffected populations is limited to increasing the detection rate. Because chromosomal defects have variable exhibitions, amniocentesis utilization is still a choice for screen-positive pregnancies. Screen-positive pregnancies had increased risk of chromosomal abnormalities.展开更多
Objective:To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA). Methods:The cells from human fetal cerebellum (8-10 weeks of gestation) were grown and ...Objective:To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA). Methods:The cells from human fetal cerebellum (8-10 weeks of gestation) were grown and expanded in vitro. The cultured neurospheres were then implanted into the dentate nuclei of patients by stereo tactic operation. Totally,12 patients (7 males and 5 females with age ranging 22-62 years,mean 43 years) were treated by this operation from August 2006 to August 2008. Results:The cells of fetal cerebellum were expanded by 107 folds in undifferentiated state in the culture. After the operation,no rejection was detected. Follow up,the effective rates were 58.3% after 3 months,75.0% after 6 months,and 66.7% for 12-24 months (mean 18 months). Conclusion:the transplantation of in vitro cultured neural stem cell is a feasible and effective treatment for inherited CA,but the long term effectiveness need to be taken in consideration.展开更多
Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 differe...Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 different human diseases, which superficially seem to share little with one another, result from LMNA mutations. The position of the mutation within LMNA appears to be associated with the phenotypes. This review gives an overview of genotype-phenotype relationship and describes recent advances in animal models and pathogenic mechanisms.展开更多
Experimental RNA interference (RNAi) leading to the selective knockdown of gene function is induced by introducing into cells either double stranded RNA (dsRNA), or short interfering RNA (siRNA) fragments into which d...Experimental RNA interference (RNAi) leading to the selective knockdown of gene function is induced by introducing into cells either double stranded RNA (dsRNA), or short interfering RNA (siRNA) fragments into which dsRNA is cut. The siRNA triggers degradation of homologous messengerRNA (mRNA). Widely used as a research tool in the genetic model organisms Caenorhabditis elegans, Drosophila melanogaster and mouse to investigate the function of individual genes, RNAi has also been deployed in genome-wide, specific gene-knockdown screens. Recent rapid progress in the application of RNAi to mammalian cells, including neurons and muscle cells, offers new approaches to drug target identification and validation.Advances in targeted delivery of RNAi-inducing molecules have raised the possibility of using RNAi directly as a therapy for a variety of human genetic and other neural and neuromuscular disorders. Here, we review examples of the application of RNAi to worm, fly and mouse models of such diseases aimed at understanding their pathophysiology.展开更多
In 1975, the American Society of Human Genetics adopted the following definition of genetic counseling: ge-netic counseling is a communication process which deals with the human problems associated with the occurrence...In 1975, the American Society of Human Genetics adopted the following definition of genetic counseling: ge-netic counseling is a communication process which deals with the human problems associated with the occurrence orrisk of occurrence of a genetic disorder in a family. This definition indicates that genetic counseling is the deliveryof information about genetic diseases, including genetic risks, natural history of the disease, and clinical manage-ment of the disease, to patients and their families. Although genetic counseling is not a newword for both westerncountries and China, the development of which is quite different. Many excellent genetic counseling programs havebeen developed since then in developed countries, whereas there is no formal one in China. In the United States,professionals who carry outgenetic counseling musthave taken a professional training and have had the certificate ofAmerican Board of Genetic Counseling (ABGC) (www.abgc.net).展开更多
Charcot-Marie-Tooth disease (CMT) affects the peripheral nervous system. It is generally inherited in an autosomal dominant pattern, but also is inherited in recessive or an X-linked pattern. The degree of severity ca...Charcot-Marie-Tooth disease (CMT) affects the peripheral nervous system. It is generally inherited in an autosomal dominant pattern, but also is inherited in recessive or an X-linked pattern. The degree of severity can vary greatly from patient to patient, even within the same family. Traditionally, the different classes of CMT have been divided into demyelinating forms and axonal forms. Until 10 years ago, the genetic basis of CMT disease was largely unknown. An intrachromosomal duplication on chromosome 17 was found in 1991, and a point mutation in the peripheral myelin protein-22 gene was discovered in 1992. The work starts a new stage of the molecular basis of this large group of peripheral neuropathies. In this review, we will summarize what is known today about the genetics of CMT, and what we have learned about the underlying disease mechanisms.展开更多
Objective: To intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. Methods: Twelve exons of the LMNA gene were amplified from genetomic ...Objective: To intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. Methods: Twelve exons of the LMNA gene were amplified from genetomic DNA. PCR products of each exon were analyzed by single strand conformational polymorphism (SSCP). Results: No abnormal SSCP pattern, suggesting no mutation in our CMT patients, was detected. Conclusion: The CMT diseases resulted from the mutations of LMNA gene were rare.展开更多
Objective: To evaluate the frequency of MSI in epithelial ovarian tumors and its relationship with clinicopathologic features. Methods: Ninety fresh specimens of epithelial ovarian tumors, including 74 primary and 16 ...Objective: To evaluate the frequency of MSI in epithelial ovarian tumors and its relationship with clinicopathologic features. Methods: Ninety fresh specimens of epithelial ovarian tumors, including 74 primary and 16 secondary tumors, were collected. Microsatellite analysis was carried out using 5 mono- and dinucleotide markers from the National Cancer Institute Consensus Panel by fluorescence-labeled polymerase chain reaction. Results: Of 90 epithelial ovarian tumors analyzed, 18 demonstrated a high level of microsatellite instability (MSI-H), 30 demonstrated a low level of microsatellite instability (MSI-L), and the remaining 42 exhibited microsatellite stability (MSS). Frequency of microsatellite instability (MSI) at loci BAT-25 was higher than that at any other loci. No correlation was found between MSI level and patient age, tumor type, tumor differentiation (P>0.05). But the microsatellite instability-high phenotype correlates with clinical stage.It tended to occur more frequently in early-stage tumors (P=0.03). Conclusion: The frequent MSI in epithelial ovarian tumors suggests that it is an early event to involve in the development of epithelial ovarian tumors.展开更多
Objective:PCBP1 is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. The protein plays a pivotal role in post-transcriptional regulatio...Objective:PCBP1 is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. The protein plays a pivotal role in post-transcriptional regulation for RNA metabolism and RNA function in gene expression. We hypothesized and were going to identify that the regulatory function of PCBP1 is performed through different complexes of proteins that include PCBP1. Methods:To test our hypothesis,approaches of protein wal-king with a yeast two-hybrid system (Y2H),pulling down in yeasts,co-immunoprecipitation and immunofluorescent microscopy assay were employed in this study. The PCBP1 was used as the initial "walker" to search for its interaction partner(s). Results:Candidate proteins including MYL6,PECAM1,CSH1,RAB7,p57KIP2,ACTG1,RBMS1 and PSG4-like were identified with selection mediums and preceding methods. Conclusion:With these candidate protein molecules,some protein complexes associating with PCBP1 are proposed,which may help in a better understanding of physiological functions of PCBP1 and proved evidence that PCBP1 is involved in variant biological pathways.展开更多
Dystonia is a syndrome which is characterized by sustained muscle contractions, producing twisting, repetitive, and patterned movements, or abnormal postures. According to genetic basis, dystonia is classified into 13...Dystonia is a syndrome which is characterized by sustained muscle contractions, producing twisting, repetitive, and patterned movements, or abnormal postures. According to genetic basis, dystonia is classified into 13 subtypes. We mainly discussed two subtypes, DYT1 and DYT5, in this review. Early-onset primary dystonia is caused by the mutation of DYT1 gene, which leads to TORSINA abnormal. GTP cyclohydrolase 1 (GTPCH1)-deficient DRD(DYT5) is caused by the mutations of GCH1 gene. By genetic testing, we can confirm clinical diagnosis of each subtype and develop prenatal diagnosis for it.展开更多
Autism is a neurodevelopmental disorder characterized by impairments in social skills, language, and behavior. It is now clear that autism is not a disease, but a syndrome characterized by phenotypic and genetic compl...Autism is a neurodevelopmental disorder characterized by impairments in social skills, language, and behavior. It is now clear that autism is not a disease, but a syndrome characterized by phenotypic and genetic complexity. The etiology of autism is still poorly understood. Available evidence from a variety of sources strongly suggests that many genetic disorders are frequently associated with autism for their similar phenotypes. Based on this fact, this review begins by highlighting several principal genetic syndromes consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, Pader-Willi syndrome, Rett syndrome, Down syndrome and Turner syndrome). These genetic disorders include both chromosome disorders and single gene disorders. By comparing the similar phenotype, protein marker and candidate genes, we might make some breakthrough in the mechanism of autism and other genetic disorders.展开更多
Since the sequencing of the human genome was announced in 2001, researchers have an increased ability to discern the genetic basis for diseases. This reference genome has opened the door to translational medicine whic...Since the sequencing of the human genome was announced in 2001, researchers have an increased ability to discern the genetic basis for diseases. This reference genome has opened the door to translational medicine which may be defined as the use of data acquisition and analysis to improve medical care, including prognostics, diagnostics, preventive intervention, therapeutic selection, and individualized treatment based on the complex interaction between inherited and acquired elements of human variation. It is an approach that will build on the comprehensive nature of the genome sciences. It aims at detecting and understanding of all genetic variations of the human genome that contribute to the manifestation and progression of disease.It is clear that what is really new in genomic medicine is the application of genomic technology on a large scale to virtually every problem of medicine. Genomic medicine goes well beyond the traditional boundaries of genetics in medicine. As a clinical paradigm, translational medicine provided global, comprehensive, and multidimensional treatment and management strategies based on the science emerging from the study of genomics and genetics of human diseases. Translational medicine will have a transformative role in healthcare, whose emphasis can be anticipated to dramatically shift from disease treatment to health maintenance.展开更多
文摘Objective: To investigate the efficiency of maternal serum triple screening for the genetic abnormality in second-trimester and the morbidity of adverse pregnancy outcome in false positive results of the test. Methods: A total of 4 680 pregnant women with singleton pregnancies assigned in Obs & Gyn Hospital, Fudan University, underwent triple screening test (alpha fetoprotein, AFP; human chorionic gonadotropin, HCG and unconjugated estriol, uE3) by fluorescence enzyme immunoassay between 2003 and 2005. The valid MoM (Multiples of Median) value of mid-trimester serum AFP, uE3, and hCG and risk assessments was provided by Beckman Coulter Co. when applied in the prenatal Down syndrome screening service. The study compares the incidence of chromosomal abnormalities with Down syndrome in screen positive women and compares to the MoM value established in the literature. The risks of having a fetus with congenital abnormalities or of developing obstetric complications in the screen positive women with their matched controls.Results:The MoM values for the triple tests of our study are similar to established values of literature. Only 51.01% women with pregnancies agree to receive screening. Amniocentesis utilization rate was 55.12% in the screen-positive pregnancies. The false positive rate was 6.89% and the median of maternal age of the women was 28.13 (range 19 to 49) years old. Chromosomal abnormalities were identified in 21 pregnancies, including 9 cases of trisomy 21.The detection rate was 77.77%. Pregnancies with positive screening results had a significantly higher risk of adverse outcomes than those with negative results (P< 0.05). Whereas there was no difference in the incidences of fetal congenital appearance or skeleton abnormality. Conclusion: Adjusting MoM values of local unaffected populations is limited to increasing the detection rate. Because chromosomal defects have variable exhibitions, amniocentesis utilization is still a choice for screen-positive pregnancies. Screen-positive pregnancies had increased risk of chromosomal abnormalities.
文摘Objective:To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA). Methods:The cells from human fetal cerebellum (8-10 weeks of gestation) were grown and expanded in vitro. The cultured neurospheres were then implanted into the dentate nuclei of patients by stereo tactic operation. Totally,12 patients (7 males and 5 females with age ranging 22-62 years,mean 43 years) were treated by this operation from August 2006 to August 2008. Results:The cells of fetal cerebellum were expanded by 107 folds in undifferentiated state in the culture. After the operation,no rejection was detected. Follow up,the effective rates were 58.3% after 3 months,75.0% after 6 months,and 66.7% for 12-24 months (mean 18 months). Conclusion:the transplantation of in vitro cultured neural stem cell is a feasible and effective treatment for inherited CA,but the long term effectiveness need to be taken in consideration.
文摘Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 different human diseases, which superficially seem to share little with one another, result from LMNA mutations. The position of the mutation within LMNA appears to be associated with the phenotypes. This review gives an overview of genotype-phenotype relationship and describes recent advances in animal models and pathogenic mechanisms.
文摘Experimental RNA interference (RNAi) leading to the selective knockdown of gene function is induced by introducing into cells either double stranded RNA (dsRNA), or short interfering RNA (siRNA) fragments into which dsRNA is cut. The siRNA triggers degradation of homologous messengerRNA (mRNA). Widely used as a research tool in the genetic model organisms Caenorhabditis elegans, Drosophila melanogaster and mouse to investigate the function of individual genes, RNAi has also been deployed in genome-wide, specific gene-knockdown screens. Recent rapid progress in the application of RNAi to mammalian cells, including neurons and muscle cells, offers new approaches to drug target identification and validation.Advances in targeted delivery of RNAi-inducing molecules have raised the possibility of using RNAi directly as a therapy for a variety of human genetic and other neural and neuromuscular disorders. Here, we review examples of the application of RNAi to worm, fly and mouse models of such diseases aimed at understanding their pathophysiology.
文摘In 1975, the American Society of Human Genetics adopted the following definition of genetic counseling: ge-netic counseling is a communication process which deals with the human problems associated with the occurrence orrisk of occurrence of a genetic disorder in a family. This definition indicates that genetic counseling is the deliveryof information about genetic diseases, including genetic risks, natural history of the disease, and clinical manage-ment of the disease, to patients and their families. Although genetic counseling is not a newword for both westerncountries and China, the development of which is quite different. Many excellent genetic counseling programs havebeen developed since then in developed countries, whereas there is no formal one in China. In the United States,professionals who carry outgenetic counseling musthave taken a professional training and have had the certificate ofAmerican Board of Genetic Counseling (ABGC) (www.abgc.net).
文摘Charcot-Marie-Tooth disease (CMT) affects the peripheral nervous system. It is generally inherited in an autosomal dominant pattern, but also is inherited in recessive or an X-linked pattern. The degree of severity can vary greatly from patient to patient, even within the same family. Traditionally, the different classes of CMT have been divided into demyelinating forms and axonal forms. Until 10 years ago, the genetic basis of CMT disease was largely unknown. An intrachromosomal duplication on chromosome 17 was found in 1991, and a point mutation in the peripheral myelin protein-22 gene was discovered in 1992. The work starts a new stage of the molecular basis of this large group of peripheral neuropathies. In this review, we will summarize what is known today about the genetics of CMT, and what we have learned about the underlying disease mechanisms.
文摘Objective: To intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. Methods: Twelve exons of the LMNA gene were amplified from genetomic DNA. PCR products of each exon were analyzed by single strand conformational polymorphism (SSCP). Results: No abnormal SSCP pattern, suggesting no mutation in our CMT patients, was detected. Conclusion: The CMT diseases resulted from the mutations of LMNA gene were rare.
文摘Objective: To evaluate the frequency of MSI in epithelial ovarian tumors and its relationship with clinicopathologic features. Methods: Ninety fresh specimens of epithelial ovarian tumors, including 74 primary and 16 secondary tumors, were collected. Microsatellite analysis was carried out using 5 mono- and dinucleotide markers from the National Cancer Institute Consensus Panel by fluorescence-labeled polymerase chain reaction. Results: Of 90 epithelial ovarian tumors analyzed, 18 demonstrated a high level of microsatellite instability (MSI-H), 30 demonstrated a low level of microsatellite instability (MSI-L), and the remaining 42 exhibited microsatellite stability (MSS). Frequency of microsatellite instability (MSI) at loci BAT-25 was higher than that at any other loci. No correlation was found between MSI level and patient age, tumor type, tumor differentiation (P>0.05). But the microsatellite instability-high phenotype correlates with clinical stage.It tended to occur more frequently in early-stage tumors (P=0.03). Conclusion: The frequent MSI in epithelial ovarian tumors suggests that it is an early event to involve in the development of epithelial ovarian tumors.
基金Supported in part by the “985” program(985-2-035-39) of the Chinese Ministry of Education“973” project(2007CB511902)of the Chinese Ministry of Sciences and Technology+1 种基金National Nature Science Foundation(30671157)the NewYork State Office of Mental Retardation and Developmental Disabilities(NYSOMRDD)~~
文摘Objective:PCBP1 is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. The protein plays a pivotal role in post-transcriptional regulation for RNA metabolism and RNA function in gene expression. We hypothesized and were going to identify that the regulatory function of PCBP1 is performed through different complexes of proteins that include PCBP1. Methods:To test our hypothesis,approaches of protein wal-king with a yeast two-hybrid system (Y2H),pulling down in yeasts,co-immunoprecipitation and immunofluorescent microscopy assay were employed in this study. The PCBP1 was used as the initial "walker" to search for its interaction partner(s). Results:Candidate proteins including MYL6,PECAM1,CSH1,RAB7,p57KIP2,ACTG1,RBMS1 and PSG4-like were identified with selection mediums and preceding methods. Conclusion:With these candidate protein molecules,some protein complexes associating with PCBP1 are proposed,which may help in a better understanding of physiological functions of PCBP1 and proved evidence that PCBP1 is involved in variant biological pathways.
文摘Dystonia is a syndrome which is characterized by sustained muscle contractions, producing twisting, repetitive, and patterned movements, or abnormal postures. According to genetic basis, dystonia is classified into 13 subtypes. We mainly discussed two subtypes, DYT1 and DYT5, in this review. Early-onset primary dystonia is caused by the mutation of DYT1 gene, which leads to TORSINA abnormal. GTP cyclohydrolase 1 (GTPCH1)-deficient DRD(DYT5) is caused by the mutations of GCH1 gene. By genetic testing, we can confirm clinical diagnosis of each subtype and develop prenatal diagnosis for it.
文摘Autism is a neurodevelopmental disorder characterized by impairments in social skills, language, and behavior. It is now clear that autism is not a disease, but a syndrome characterized by phenotypic and genetic complexity. The etiology of autism is still poorly understood. Available evidence from a variety of sources strongly suggests that many genetic disorders are frequently associated with autism for their similar phenotypes. Based on this fact, this review begins by highlighting several principal genetic syndromes consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, Pader-Willi syndrome, Rett syndrome, Down syndrome and Turner syndrome). These genetic disorders include both chromosome disorders and single gene disorders. By comparing the similar phenotype, protein marker and candidate genes, we might make some breakthrough in the mechanism of autism and other genetic disorders.
文摘Since the sequencing of the human genome was announced in 2001, researchers have an increased ability to discern the genetic basis for diseases. This reference genome has opened the door to translational medicine which may be defined as the use of data acquisition and analysis to improve medical care, including prognostics, diagnostics, preventive intervention, therapeutic selection, and individualized treatment based on the complex interaction between inherited and acquired elements of human variation. It is an approach that will build on the comprehensive nature of the genome sciences. It aims at detecting and understanding of all genetic variations of the human genome that contribute to the manifestation and progression of disease.It is clear that what is really new in genomic medicine is the application of genomic technology on a large scale to virtually every problem of medicine. Genomic medicine goes well beyond the traditional boundaries of genetics in medicine. As a clinical paradigm, translational medicine provided global, comprehensive, and multidimensional treatment and management strategies based on the science emerging from the study of genomics and genetics of human diseases. Translational medicine will have a transformative role in healthcare, whose emphasis can be anticipated to dramatically shift from disease treatment to health maintenance.
