耳聋基因的筛查与诊断

先天性耳聋是人类最常见的出生缺陷之一,发病率约为1‰～3‰,这一数据在某些地区还有进一步增高的趋势[1-3],其中50%以上由遗传因素所导致[4-5]。根据遗传方式的不同,遗传性耳聋可分为显性遗传(约占20%～30%)、隐性遗传(约占60%～70%)、X连锁遗传(约占2%)和线粒体遗传(小于     

Molecular biological diagnosis

Biological behavior of lung cancer was evaluated by basic study. Malignancy Associated Change is the concept that the nuclear features of normal cells in the vicinity of cancer show subtle morphological difference from those of healthy individuals. The difference was recognized by high resolution cytometry and the expression of MAC cells was correlated with the degree of abnormality of chest diseases. Comparative genomic hybridization and fluorescence in situ hybridization were performed to investigate genetic abnormality of. Multiple genetic abnormalities and chromosomal instability showed poor prognosis. Two dimensional electrophoresis was employed to detect the expression of the specific protein of lung cancer. TAO2 was proved to be specific to well differentiated adenocarcinoma. Also, metabolic analysis will be employed for cell analysis.     

Molecular diagnosis of leishmaniasis

This review describes the worldwide situation of visceral and tegumentary leishmaniasis with an emphasis on diagnosis, including methods for the detection of antibodies, antigens, parasite DNA and of skin testing. The advantages and problems of each method are discussed and the need for a rapid, sensitive and low-cost diagnostic method for use in field conditions is highlighted. Recent advances in Leishmania genome sequencing, the use of DNA microarrays and protein microarray methodologies and their potential use for leishmaniasis diagnosis are presented.     

Molecular diagnosis of mycobacteria

Tuberculosis is one of the leading infectious diseases in the world and is responsible for more than 2 million deaths and 8 million new cases annually. Because of the slow growth rate of the causative agent Mycobacterium tuberculosis, isolation, identification, and drug susceptibility testing of this organism and other clinically important mycobacteria can take several weeks or longer. During the past several years, many molecular methods have been developed for direct detection, species identification, and drug susceptibility testing of mycobacteria. These methods can potentially reduce the diagnostic time from weeks to days. Currently, two nucleic acid amplification methods, the Enhanced Mycobacterium tuberculosis Direct Test (Gen-Probe) and the Amplicor Mycobacterium tuberculosis Test (Roche Diagnostic Systems), have been approved by the Food and Drug Administration for direct detection of M. tuberculosis from clinical specimens. PCR-based sequencing has become commonly used to identify many mycobacterial species. DNA probes have been widely used for species determination of the most commonly encountered mycobacteria. High-density oligonucleotide arrays (DNA microarrays) also have been applied to simultaneous species identification and detection of mutations that confer rifampin resistance in mycobacteria.     

Molecular diagnosis of leukemia

The diagnosis of leukemia relies upon a multiparametric approach involving a number of different pathology disciplines. Molecular methods are increasingly employed to help refine diagnosis, establish prognosis and determine the most appropriate treatment, including rational therapies targeting the underlying genetic lesion. This review aims to highlight some of the molecular techniques commonly used in the diagnosis of leukemia using relevant examples. The focus is on procedures in current use and technologies showing promise in the research setting that are likely to enter clinical use in the near future. The list is not exhaustive, and this article concentrates on diagnosis of leukemia; techniques used to monitor response to therapy and molecular residual disease are mentioned but have not been covered extensively.     

Molecular diagnosis of Epstein-Barr virus

Molecular techniques have become an important tool in Epstein-Barr virus diagnostics. In recent years novel real-time PCR formats and in situ techniques have been developed that offer increased time efficiency, reduced cross-contamination, high reproducibility, high sensitivity and allow determination of viral loads. In the near future, widespread clinical application of these diagnostic modalities may provide increased knowledge of the pathophysiology of Epstein-Barr virus infection and may optimize treatment or even explore novel Epstein-Barr virus-related diseases. The monitoring of Epstein-Barr virus viral loads in different tissue compartments is currently being effectively used to assess the treatment response or prognosis in patients with oncological diseases or immunosuppression. This may also gain increasing importance in the nononcological environment. However, the general acceptance of molecular techniques will largely depend on improved standardization.     

染色体病的分子诊断

染色体数目或者结构的异常是导致染色体病的物质基础。随着人类基因组计划(HGP)的成功完成以及结构基因组学、功能基因组学等学科的发展,高通量测序、PCR技术、生命科学领域的基因芯片技术与生物信息学技术相结合,使染色体病的研究日益深入,染色体病的检测方法也日益增多。新的分子诊断技术以其高灵敏度、高准确性和高通量的特点在染色体疾病的检验和诊断中应用越来越广泛,目前已逐步与传统的细胞遗传学分析相互结合、互为印证,共同实现对染色体疾病的实验室诊断。该文就染色体病的分子诊断技术及临床应用进行述评。     

Molecular diagnosis of cystic fibrosis

A review of the current molecular diagnosis of cystic fibrosis including an introduction to cystic fibrosis, the gene function, the phenotypic variation, who should be screened for which mutation, newborn and couple screening, quality assurance, phenotype-genotype correlation, methods and method limitations, options, statements, recommendations, useful Websites and treatments.     

Molecular diagnosis of solid tumors

This review highlights three examples of novel targeted therapeutics for solid tumors that are currently approved in Japan: 1) Trastuzumab (Herceptin) for patients with metastatic breast cancer that demonstrates overexpression of HER2/neu; 2) Imatinib mesylate (Glivec) for patients with gastrointestinal tumors, of which tumor cells express c-Kit; and 3) Gefitini (Iressa) for patients with advanced non-small cell lung cancers, which response to gefitinib is recently suggested to be associated with EGFR mutation. In these molecular targeted therapies, diagnostic tools to verify the presence of an appropriate molecular target is crucial to the success, and thus the methods and its interpretation are discussed in this review.     

Molecular diagnosis of pancreas carcinoma

Cellular protooncogenes, tumor suppressor genes (antioncogenes), and DNA mismatch repair mutators are generally the key molecular genetic biomarkers undergoing alterations during carcinogenesis, i.e., activation of oncogenes, inactivation of tumor suppressors, and DNA mismatch repair gene defects are essential events in cancer causation. In pancreas cancer, high incidence of oncogene K-ras point mutations at the codon 12th is associated with premalignant and malignant transformation. Mutation in p53 tumor suppressor is also detected in pancreas adenocarcinoma. Concurrent loss of p53 and K-ras function may contribute to the clinical aggressiveness of pancreas cancer. Microsatellite instability and DNA mismatch repair defects may represent new mutator phenotype for pancreas carcinogenesis. Mutation of cell cycle regulators, such as inhibitor of CDK4 or p16 tumor suppressor gene, is a new molecular event in pancreas cancer. Mutation of cyclin-dependent kinases also may be involved in pancreas carcinogenesis. Loss or mutation of a new candidate tumor suppressor, DPC4 (deleted in pancreas carcinoma locus 4), is reported in pancreas cancer. The protein products of these gene mutations are potential tumor antigens, thus genotype expression can be detected by phenotype. Most of these emerging molecular genetic biomarkers are associated with regulation of cell growth and recognition, as well as gene expression, and may offer new insight into the cellular precursors to and genesis of pancreas cancer. J. Clin. Lab. Anal. 11:225–231, 1997. © 1997 Wiley-Liss, Inc.     

Molecular diagnosis of myocardial disease

Myocardial disorders are major causes of morbidity and mortality, including heart failure, sudden death and the need for heart transplantation. The two most common forms of myocardial disorders, dilated cardiomyopathy and hypertrophic cardiomyopathy are paradigms of left ventricular systolic dysfunction and diastolic dysfunction. The genetics of these disorders are increasingly understood with the sarcomere playing a central role in the development of HCM and the link between sarcomere and sarcolemma being key to the development of DCM. In this review, the genetics of the myocardial diseases will be described.     

Molecular diagnosis of inherited diseases

The importance of the interaction between basic science and clinical practice has long been known but it has become even more evident in the past few decades with the impressive rate of development in the field of molecular genetics. This short article reviews molecular diagnosis of two different diseases for which scientific progress has immediately been translated into a dramatic improvement of the quality of medical care: the Fragile X Syndrome, paradigm of the new mutational mechanism of the unstable triplet repeats, and von Hippel-Lindau disease, a recent acquisition in the growing number of familial cancer syndromes.     

恶性肿瘤的分子诊断技术

恶性肿瘤的分子诊断主要依赖于肿瘤标志物的检测,肿瘤标志物主要分为胚胎类肿瘤标志物、糖类抗原肿瘤标志物、酶类肿瘤标志物、激素类肿瘤标志物及其他非特异性的肿瘤标志物。目前临床中,肿瘤标志物在肿瘤筛查、肿瘤诊断和鉴别诊断中具有重要作用,但由于假阳性和假阴性的存在,敏感性和特异性均较低,使肿瘤标志物的临床应用具有一定局限性,其检测结果不能单独作为肿瘤的诊断依据。随着分子生物学技术的发展,新的肿瘤标志物的不断发现,肿瘤的分子诊断技术将会不断提高。     

CT和MRI诊断儿童先天性耳聋的对比

目的 对比先天性耳聋患儿的宝石CT和MRI特点。方法 回顾性分析60例临床诊断的先天性耳聋患儿的宝石CT及MRI资料,将原始数据传至配套工作站,采用MIP、MRP、VR进行重建,分析两种检查的一致性。结果 CT显示耳部骨性结构具有优势,MRI显示耳部神经具有优势。2种检查对于显示乳突炎并大前庭导水管综合征、大前庭导水管综合征及耳蜗半规管畸形的一致性较好（Kappa>0.75）,显示半规管狭窄的一致性尚可（Kappa=0.485）。结论 CT、MR检查诊断儿童先天性耳聋各有优势,可优势互补,具有重要的临床应用价值。     

Molecular biology diagnosis in oncology

The applications of molecular biology diagnosis in oncology are presented and discussed. These are: improved nosologic definition; diagnosis of clonality; definition of new prognosis subgroups in some cancers; as an aid in bone marrow transplantation follow-up; diagnosis of the residual disease; early diagnosis of cancer; evaluation of individual cancer risk.     

Molecular diagnosis of facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited neuromuscular disorder after Duchenne muscular dystrophy and myotonic dystrophy. The gene underlying FSHD was mapped to chromosome 4q35 in 1990 and was shown to be closely linked to locus D4F104S1. Although D4F104S1-associated deletions are closely associated with FSHD, the identity and location of the FSHD gene (or genes) still remain elusive, as does the mechanistic basis of the disease. In addition, although approximately 5% of FSHD families fail to exhibit linkage to 4q35, a putative second locus remains unidentified. The search for the FSHD gene has been hampered both by sequence homologies between the 4q35 candidate region and other chromosomal regions and by the presence of many highly repetitive sequences. Molecular diagnosis for FSHD is usually offered with 98% accuracy but because of its complexity, a much more simple test would be preferable. Indeed, the identification of the FSHD gene itself should potentiate major improvements in diagnostic testing.