Objective: Duchenne and Becker muscular dystrophy (DMD/BMD) is an X-linked lethal recessive disease caused by mutations in the dystrophy gene. There is no efficient treatment for this serious and disabling disease. We established a combination method to detect carriers and perform prenatal diagnosis. Methods: In our study, from 1994 to 2005, using a different combination of 5 methods, including SRY gene amplification, multiplex PCR, multiplex Fluorescence PCR capillary electrophoresis, multiplex ligation-dependent probe amplification (MLPA) and linkage analysis of short tandem repeats (STR), 36 prenatal diagnosis were performed for pregnancies at risk of having a DMD/BMD baby through amniocentesis. Results: Fourteen out of 21 male fetuses were found to be affected and respective pregnancies were terminated. A combined diagnostic rate of 83% was achieved for 30 cases with deletions, duplications, and non-deletion mutations after tested by more than one method. Conclusion: Using a combined method, we can diagnoses patients and carriers in DMD families, and perform prenatal diagnosis for the risk fetus. MLPA provides a simple, rapid and accurate method for deletions and duplications of all the 79 DMD exons. MLPA method for DMD diagnosis is the first report in our country.
作者：黎青；李少英；胡冬贵；孙筱放；陈敦金；张成；蒋玮莹 刊期： 2006年第01期
Objective: To study the frequency of interstitial 7q deletions in B-cell lymphoproliferative disorders (B-LPDs). Methods: Cases were collected from the clinical laboratory diagnosis database at USLabs/LabCorp over the past two years (2002 to 2004). Cases that showed deletions in the long arm of chromosome 7 were then reviewed. Interstitial deletions in the long arm of chromosome 7 were further investigated according to the indications for clinical laboratory studies and flow cytometry findings. The final clinical diagnosis for each case was obtained from the referring physician. Results: A total of 19 483 cases were included in this series. Eighty-five cases were observed to have either terminal or interstitial deletion in the long arm of chromosome 7. Of the 85 cases, 46 had interstitial deletions accounting for 54.1% of the 7q deletions combined. B-LPDs were found in 10 of the 46 cases, accounting for 21.7%. The B-LPDs associated with 7q interstitial deletions were diverse, including B-cell chronic lymphocytic leukemia (B-CLL) in five cases. The deleted region in the long arm of chromosome 7 in the 10 cases associated with B-LPDs was solely confined to the 7q22-q32 region. Conclusion: (1) The frequency of 7q interstitial deletions associated with B-LPDs is substantially high; (2) 7q interstitial deletions are not uncommon in B-CLL.
作者： 刊期： 2006年第01期
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.
作者： 刊期： 2006年第01期
Objective: To extract the relevant SNPs for alcoholism using sib-pair IBD profiles of pedigrees.Methods: We used the ensemble decision approach, a supervised learning approach based on decision forests, to locate alcoholism relevant SNPs using genome-wide SNP data. Results: Application to a publicly available large dataset of 100 simulated replicates for three American populations (http://www.gaworkshop.org/) demonstrates that the proposed approach has successfully located all of the simulated true loci.Conclusion: The numerical results establish the proposed decision forest analysis to be a powerful and practical alternative for large-scale family-based association study.
作者：李霞；饶绍奇；张薇；郭政；姜伟；杜磊 刊期： 2006年第01期
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.
作者：宋书娟；章远志；陈彪；王曼捷；王越英；张远锦；闫明；Nanbert ZHONG 刊期： 2006年第01期
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.
作者：卢媛；刘惜时；王跃祥；宋后燕；Nanbert ZHONG 刊期： 2006年第01期
Objective:This study investigated the prognostic significance of age at diagnosis, stage, tumor subtype, pelvic lymph node metastasis (PLNM), lymph-vascular space involvement (LVSI), presence or absence of deep cervical stromal invasion (DCSI) in stage ⅠB-ⅡA cervical cancer patients. It also investigated the inter-relationship among these factors. Methods: 152 patients treated with radical hysterectomy plus pelvic lymphadenectomy were followed up for a median of 49 months and were evaluated retrospectively. Results: The 5-year overall survival rate was 84.8%. The distribution of age at diagnosis is of bimodal shape, peaking at 42 and 68 years, respectively. Tumor subtype, PLNM, DCSI, and LVSI were found to be significant prognostic factors individually. After multivariate analysis, only tumor subtype and PLNM were found to be independent, significant prognostic factors for survival. The prognostic importance of LVSI appeared to be eclipsed by the presence of PLNM. DCSI was statistically related with FIGO stage, LVSI and PLNM. Conclusion: Tumor subtype and PLNM are the two most important independent prognostic factors for stages ⅠB-ⅡA cervical cancer. Some prognostic factors are inter-related and may reflect different facets of tumor progression.
作者：刘惜时；易晓芳；赵敏；郭孙伟 刊期： 2006年第01期
Objective:To compare the therapeutic and toxic profile of topotecan given intraperitoneally with intravenously in human ovarian cancer xenografted into athymic nude mice.Methods: Eighty female Balb-c/nu-nu mice were randomized assigned into eight groups (n=10). Xeneografts resulted from intramesentery injection of cultured human ovarian cancer cells SKOV3 in athymic mice. Onset of intraperitoneal treatment with either topotecan or cisplatin (7.5 mg/kg) was on day 7. Animals scheduled for topotecan i.p. received intraperitoneal application of topotecan (1.5 mg/kg×2, 3.0 mg/kg×2, 6.0 mg/kg×2 or 10.0 mg/kg×1). Animals scheduled for topotecan i.v. received intravenous administration of topotecan (6.0 mg/kg×2 or 10.0 mg/kg×1). Two weeks after drug application animals were killed. Tumor growth inhibition were assessed and compared with untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity was determined by loss of body weight. Cell cycle division and apoptosis after drug administration was determined by flow cytometric analysis.Results: In a panel of ten tumour xenografts, intraperitoneal topotecan was significantly more effective than intravenous administration. The toxicity profile suggested a better tolerability in terms of weight loss after intraperitoneal administration than cisplatin control. Topotecan 10.0 mg/kg i.p. per day (1 day) schedule was an optimal treatment for ovarian cancer and well tolerated by mice with no signs of acute toxicity. Topotecan and cisplatin induce cells G0-G1 arrest and apparent apoptosis. No significant difference among mice treated with topotecan intraperitoneally or intravenously or cisplatin was observed in term of apoptosis and cell cycle perturbation.Conclusion:The results may have implications for the future design of clinical studies on intraperitoneal application of topotecan. It suggests that apoptosis and cell cycle perturbation play an limited role in the mechanism of topotecan administration.
作者：易晓芳；范士明；姚明；丰有吉 刊期： 2006年第01期
Objective: To develop novel strategies to identify relevant molecular signatures for complex human diseases based on data of identical-by-decent profiles and genomic context.Methods: In the proposed strategies, we define four relevancy criteria for mapping SNP-phenotype relationships-point-wise IBD mean difference, averaged IBD difference for window, Z curve and averaged slope for window.Results: Application of these criteria and permutation test to 100 simulated replicates for two hypothetical American populations to extract the relevant SNPs for alcoholism based on sib-pair IBD profiles of pedigrees demonstrates that the proposed strategies have successfully identified most of the simulated true loci.Conclusion: The data mining practice implies that IBD statistic and genomic context could be used as the informatics for locating the underlying genes for complex human diseases. Compared with the classical Haseman-Elston sib-pair regression method, the proposed strategies are more efficient for large-scale genomic mining.
作者：李传星；杜磊；李霞；宫滨生；张杰；饶绍奇 刊期： 2006年第01期
We report an apparently benign familial 9p subtelomere deletion identified using chromosome-arm-specific subtelomere probes in a patient with multiple congenital anomalies. Our experience demonstrated that the discovery of a subtelomeric deletion and/or duplication does not always guarantee the identification of the etiology for the patient's phenotype and a positive finding with subtelomere probes should always be followed by parental study with the same probe in order to distinguish a disease causing alteration from a benign familial polymorphism.
作者： 刊期： 2006年第01期
Genetic tests for about 1 000 health conditions have been developed, of which more than 600 are currently available for clinical testing[1]. Many genetic tests identify DNA variants; others measure biochemical markers or analyze chromosomes. Most are used for diagnosis of rare single-gene disorders or chromosome abnormalities, and a few are used for newborn screening[2]. A growing number of genetic tests may have population-based applications. This includes determining the risk of developing a disease or condition in the future (e.g., predictive testing for breast cancer or cardiovascular disease), and recognizing genetic variations that can influence response to medicines (pharmacogenomics). These genetic tests, therefore, have the potential for broad public health impact.
作者： 刊期： 2006年第01期
1 The history and main problems in prenatal diagnosis and clinical diagnosis of inherited diseasesPrenatal diagnosis is to diagnose the fetal congenital defects and inherited diseases. In the earlier 1970s, the group of prenatal diagnosis in Peking Union Hospital was founded by Dr. Qiao-zhi LIN.Meanwhile, under the leadership of Dr. LIN, the group successfully completed the culture of amniotic fluid cells and began to diagnose fetal chromosomal diseases in the second trimester of pregnancy. In 1988, they succeeded in diagnosing chromosomal diseases by taking the chorionic villus in the early pregnancy. Since then, the genetic and prenatal counseling to those women who previously had children with severe defects were gradually developed. The work of the Peking Union Hospital developed prenatal diagnosis in our country.
作者：王斌 刊期： 2006年第01期
As the completion of human genome project, application of the knowledge and techniques developed during the past decade to the medical practice become more and more important and gain more and more attention. It is worthwhile to look back to the step prints of the development of medical genetics in China.
作者：黄尚志；高翼之 刊期： 2006年第01期
In 1975, the American Society of Human Genetics adopted the following definition of genetic counseling: genetic counseling is a communication process which deals with the human problems associated with the occurrence or risk of occurrence of a genetic disorder in a family. This definition indicates that genetic counseling is the delivery of information about genetic diseases, including genetic risks, natural history of the disease, and clinical management of the disease, to patients and their families. Although genetic counseling is not a new word for both western countries and China, the development of which is quite different. Many excellent genetic counseling programs have been developed since then in developed countries, whereas there is no formal one in China. In the United States, professionals who carry out genetic counseling must have taken a professional training and have had the certificate of American Board of Genetic Counseling (ABGC) (www.abgc.net). The ABGC prepares and administers examinations to certify individuals who provide services in the medical genetics specialty of genetic counseling, and accredits training programs in the field of genetic counseling. There are more than two dozen master degree programs of genetic counseling accredited by the ABGC with either full, interim, or recognized new programs (www.abgc.net). There are twenty-one full credential programs in the United States, three in Australia, three in Canada and two in United Kingdom (www.abgc.net). Looking through all over the China, there is no any official genetic counseling program, so neither any professional genetic counselor. Genetic counseling in China now is not offered by professionally trained genetic counselors, but clinicians such as pediatricians or obstetricians[1]. These clinicians who performing genetic counseling in China have not been trained professionally on genetic counseling. Further more, there is no any board to certificate counselors.
作者：章远志；Nanbert ZHONG 刊期： 2006年第01期
As a geographically integral part of south China, the population mix of Hong Kong is largely influenced by its location. In the past 150 years, its population has increased from a few thousand to 5.7 million. This is the result of episodic influxes of a great mass of people from China, often associated with political upheavals or economic crisis. It explains a population structure of 95% Chinese. This structure is also reflected in the finding of genetic variants in this population, which bears resemblance to neighbouring regions in China. For example, the thalassaemias and lactose intolerance are common.
作者： 刊期： 2006年第01期
Mapping and identification of disease associated genes will demonstrate the genetic basis for the human genetic disorders, and provide the fundamental data for elucidation of pathogenesis mechanism of the disorders. Genetic resources, including pedigree information, blood sample, and tissues, etc., are essential materials for finding of the linked locus and gene for certain genetic disease. Genome wide scanning, positional cloning and candidate approach are most widely used methods or strategy, by which, thousands of diseases responsible genes have been identified. National laboratory of medical genetics of China (NLMG) has initiated the study on genetic resources collection, mapping and identification of disease associated gene since 1970s, here we summarize the major findings in this area achieved by NLMG.
作者：夏家辉；夏昆；潘乾；龙志高；戴和平；邬玲仟；梁德生；蔡芳 刊期： 2006年第01期
More and more hereditary diseases, including hereditary renal diseases in particular, have been diagnosed with the achievement of the Human Genome Project in the last decade and the development of biotechnology. The increased diagnosis of hereditary diseases as well as hereditary renal diseases appeared not only in case numbers but also in disease categories. Some hereditary renal diseases that are considered to be rare previously now become relatively common, because there have been much more approaches for diagnosis, such as renal pathology, biochemistry, imaging, and genetic diagnoses.
作者：丁洁 刊期： 2006年第01期
The Sino-US Joint Clinical and Molecular Laboratory (JCML) is a comprehensive clinical research laboratory with main focus on study of hematopoetic diseases including myelodysplastic syndrome, leukemias and lymphomas. The JCML is located in the Shanghai Medical College of Fudan University (formerly Shanghai Medical University) in Shanghai, China and was established as part of a large multi-center, international study of benzene health effect in China that is sponsored by the international consortium on benzene health effect.
作者：包黎明 刊期： 2006年第01期
Application of TMS technology in newborn screening has resulted in major expansion of disorder panel for metabolic diseases in recent years. This automated, multiplex testing methodology detects multiple analytes from single analysis of one blood spot, which leads to detection of 30-35 disorders of amino acids, organic acids, and fatty acids metabolism. The early identification of persons affected with inborn errors of metabolism has led to unexpected discoveries related to the natural history of the disorder or options for therapy. This article summarized (1) the basic principles of this technology and methodology. (2) Current status of application of this methodology in the United States, European countries and in China. (3) The positive impacts on the public health and advances in medical genetics. Finally (4) Challenges, issues and possible solutions. The purpose of this article aimed at introducing new technology and exploring the possibilities of implementing into developing countries where medical genetics is not developed and foreseeing the possible problems and obstacles.
作者：Chun-li YU；顾学范 刊期： 2006年第01期
The Department of Pediatrics of Peking University First Hospital has a long term of outstanding history.It was established about 60 years ago.After the division of pediatric neurology(DPN) had been established in 1960s,it had been assigned to cover genetic disorders.During the recent 20 years,efforts have been put on three aspects:(1)Pediatric neurology clinical service and education;(2)research studies of childhood epilepsies and pediatric neurogenetic disorders;and (3) development of a strong DPN team to establish a comprehensive pediatric neurological program.In this paper,we reviewed the history of the pediatric neurology division in our department,our clinical and research work and achievements for neurogenetic diseases.
作者：吴希如 刊期： 2006年第01期
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.
作者：王小竹；Nanbert ZHONG 刊期： 2006年第01期
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.
作者：侯萌；王曼捷；Nanbert ZHONG 刊期： 2006年第01期
Lysosomal storage disorders (LSDs) are genetic defects caused by lysosomal hydrolase deficiencies. These deficiencies lead to substrate accumulation affecting cells, tissues and organs. Detecting abnormal compound excretion and deficient enzymes assist diagnosis of these disorders for treatment and prevention. This mini review summarizes clinical presentations and diagnostic workup of LSDs and updates the new development in the area.
作者： 刊期： 2006年第01期
