Medical genetics, as an important component in the advanced medical practice, has touched in variant aspectsof clinical aspects. Globally, in both developed and developing countries, medical genetics is playing more a...Medical genetics, as an important component in the advanced medical practice, has touched in variant aspectsof clinical aspects. Globally, in both developed and developing countries, medical genetics is playing more andmore important roles in dealing with the public healthcare. Being a medical specialty performing diagnosis and in-tervention for genetic disorders, the medical genetics has bridged the clinical practice and basic medical sciences.It is derived, butdifferent, fromhuman genetics. The difference of which is thatthe medical genetics provides clin-ical service for medical professionals and patients; however, the human genetics focuses on investigation of geneticprinciples.展开更多
Objective:To investigate the birth defect condition in Haidian district of Beijing city,61 272 live-born infants who were delivered in Haidian Maternal and Child Health Hospital from 2003 to the March of 2009 are anal...Objective:To investigate the birth defect condition in Haidian district of Beijing city,61 272 live-born infants who were delivered in Haidian Maternal and Child Health Hospital from 2003 to the March of 2009 are analyzed. Methods:Data was collected from the hospital's medical records and from the birth defect surveillance. Results:Among the newborns studied,1 076 were found having birth defect (17.56‰). The most common birth defects are congenital heart defect,followed by dysmorphosis of external ear,polydactyly,hypospadia,cleft lip and palate. In addition,three birth defects that are not included in the birth defect surveillance list were enorchia,renal agenesis and giant hemangioma. The birth defect rates of preterm and small for gestational age infants are significantly higher than it of the term infants. The birth defect patterns for these two types of abnormal infants are distinct. Conclusion:We have determined the pattern of birth defects in Beijing,which may help in policy-making regarding the prevention and intervention of birth defects.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
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
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 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
The 4th International Conference on Birth Defects and Disa-bilities in the Developing World is being held at New Delhi,In-dia from 4th to 9th October 2009 at Hotel Le Meridien,New Delhi.Please logon to:www.icbd 2009.c...The 4th International Conference on Birth Defects and Disa-bilities in the Developing World is being held at New Delhi,In-dia from 4th to 9th October 2009 at Hotel Le Meridien,New Delhi.Please logon to:www.icbd 2009.com to register.Aproportion of travel and per diem expenses will be awarded to those whose abstracts are accepted for Oral Presentation.展开更多
Objective: Batten disease （BD）, the juvenile form of neuronal ceroid lipofuscinosis （NCLs）, is pathological characterized by finding lysosomal storage of autofluorescent lipofuscins with unique ultrastructural pro...Objective: Batten disease （BD）, the juvenile form of neuronal ceroid lipofuscinosis （NCLs）, is pathological characterized by finding lysosomal storage of autofluorescent lipofuscins with unique ultrastructural profiles. The gene underlying BD is designated CLN3 and encodes a protein, Battenin, of unknown function that localizes in lysosomes and/or mitochondria. Previously, we hypothesized that Battenin associates with other membrane protein（s） to form a membrane complex. Dysfunction of this complex could result in the pathological changes of BD, and possibly in other NCLs. Two such membranous proteins, the slow and fast Battenin-interactive proteins （BIPs and BIPf） of unknown functions, have been identified. In this study, we have characterized the functional domains of Battenin that interact with both BIP proteins. Methods: Protein-protein interactions with a yeast two-hybrid system were employed. A “deletion assay” was employed to localize the interactive segment（s）. Different lengths of cDNA sequences lacking exon 1-5 were used to express CLN3-encoded proteins lacking N-terminal segments in the yeast two-hybrid system. N-terminal exons of CLN3 were deleted with PCR-cloning strategies.Results: We eliminated the possibility of interacting domains from the exon 7-encoded region because both Battenin and mBattenin interact with the BIP proteins. We have shown that peptide sequences encoded by exons 2 and 4 of CLN3 gene include the functional domains by which Battenin interacts with the BIP proteins. Conclusion: Our studies provide evidence that the N-terminus of Battenin is the functional domain for these protein interactions.展开更多
Objective:Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL). Methods:Genetic loci CLN1-3 were analyzed in regard to age of onset, initia...Objective:Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL). Methods:Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological symptoms, and electron microscope (EM) profiles. Results: The most common initial symptom leading to a clinical evaluation was developmental delay (30%) in NCL1, seizures (42.4%) in NCL2, and vision problems (53.5%) in NCL3. Eighty-two percent of NCL1 cases had granular osmiophilic deposits (GRODs) or mixed-GROD-containing EM profiles; 94% of NCL2 cases had curvilinear (CV) or mixed-CV-containing profiles; and 91% of NCL3 had fingerprint (FP) or mixed-FP-containing profiles. The mixed-type EM profile was found in approximately one-third of the NCL cases. DNA mutations within a specific CLN gene were further correlated with NCL phenotypes. Seizures were noticed to associate with common mutations 523G>A and 636C>T of CLN2 in NCL2 but not with common mutations 223G>A and 451C>T of CLN1 in NCL1. Vision loss was the initial symptom in all types of mutations in NCL3. Surprisingly, our data showed that the age of onset was atypical in 51.3% of NCL1 (infantile form) cases, 19.7% of NCL2 (late-infantile form) cases, and 42.8% of NCL3 (juvenile form) cases.Conclusion:Our data provide an overall picture regarding the clinical recognition of classical childhood NCLs. This may assist in the prediction and genetic identification of NCL1-3 via their characteristic clinical features.展开更多
文摘Medical genetics, as an important component in the advanced medical practice, has touched in variant aspectsof clinical aspects. Globally, in both developed and developing countries, medical genetics is playing more andmore important roles in dealing with the public healthcare. Being a medical specialty performing diagnosis and in-tervention for genetic disorders, the medical genetics has bridged the clinical practice and basic medical sciences.It is derived, butdifferent, fromhuman genetics. The difference of which is thatthe medical genetics provides clin-ical service for medical professionals and patients; however, the human genetics focuses on investigation of geneticprinciples.
文摘Objective:To investigate the birth defect condition in Haidian district of Beijing city,61 272 live-born infants who were delivered in Haidian Maternal and Child Health Hospital from 2003 to the March of 2009 are analyzed. Methods:Data was collected from the hospital's medical records and from the birth defect surveillance. Results:Among the newborns studied,1 076 were found having birth defect (17.56‰). The most common birth defects are congenital heart defect,followed by dysmorphosis of external ear,polydactyly,hypospadia,cleft lip and palate. In addition,three birth defects that are not included in the birth defect surveillance list were enorchia,renal agenesis and giant hemangioma. The birth defect rates of preterm and small for gestational age infants are significantly higher than it of the term infants. The birth defect patterns for these two types of abnormal infants are distinct. Conclusion:We have determined the pattern of birth defects in Beijing,which may help in policy-making regarding the prevention and intervention of birth defects.
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 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The 4th International Conference on Birth Defects and Disa-bilities in the Developing World is being held at New Delhi,In-dia from 4th to 9th October 2009 at Hotel Le Meridien,New Delhi.Please logon to:www.icbd 2009.com to register.Aproportion of travel and per diem expenses will be awarded to those whose abstracts are accepted for Oral Presentation.
文摘Objective: Batten disease （BD）, the juvenile form of neuronal ceroid lipofuscinosis （NCLs）, is pathological characterized by finding lysosomal storage of autofluorescent lipofuscins with unique ultrastructural profiles. The gene underlying BD is designated CLN3 and encodes a protein, Battenin, of unknown function that localizes in lysosomes and/or mitochondria. Previously, we hypothesized that Battenin associates with other membrane protein（s） to form a membrane complex. Dysfunction of this complex could result in the pathological changes of BD, and possibly in other NCLs. Two such membranous proteins, the slow and fast Battenin-interactive proteins （BIPs and BIPf） of unknown functions, have been identified. In this study, we have characterized the functional domains of Battenin that interact with both BIP proteins. Methods: Protein-protein interactions with a yeast two-hybrid system were employed. A “deletion assay” was employed to localize the interactive segment（s）. Different lengths of cDNA sequences lacking exon 1-5 were used to express CLN3-encoded proteins lacking N-terminal segments in the yeast two-hybrid system. N-terminal exons of CLN3 were deleted with PCR-cloning strategies.Results: We eliminated the possibility of interacting domains from the exon 7-encoded region because both Battenin and mBattenin interact with the BIP proteins. We have shown that peptide sequences encoded by exons 2 and 4 of CLN3 gene include the functional domains by which Battenin interacts with the BIP proteins. Conclusion: Our studies provide evidence that the N-terminus of Battenin is the functional domain for these protein interactions.
文摘Objective:Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL). Methods:Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological symptoms, and electron microscope (EM) profiles. Results: The most common initial symptom leading to a clinical evaluation was developmental delay (30%) in NCL1, seizures (42.4%) in NCL2, and vision problems (53.5%) in NCL3. Eighty-two percent of NCL1 cases had granular osmiophilic deposits (GRODs) or mixed-GROD-containing EM profiles; 94% of NCL2 cases had curvilinear (CV) or mixed-CV-containing profiles; and 91% of NCL3 had fingerprint (FP) or mixed-FP-containing profiles. The mixed-type EM profile was found in approximately one-third of the NCL cases. DNA mutations within a specific CLN gene were further correlated with NCL phenotypes. Seizures were noticed to associate with common mutations 523G>A and 636C>T of CLN2 in NCL2 but not with common mutations 223G>A and 451C>T of CLN1 in NCL1. Vision loss was the initial symptom in all types of mutations in NCL3. Surprisingly, our data showed that the age of onset was atypical in 51.3% of NCL1 (infantile form) cases, 19.7% of NCL2 (late-infantile form) cases, and 42.8% of NCL3 (juvenile form) cases.Conclusion:Our data provide an overall picture regarding the clinical recognition of classical childhood NCLs. This may assist in the prediction and genetic identification of NCL1-3 via their characteristic clinical features.
