Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data are presented on several polymorphic genetic markers in 200 Greek gypsies. Polymorphic loci studied were: the ABO, MN, Rhesus, Kell and Duffy blood groups, hemoglobin, and ceruloplasmin. A survey for congenital malformations and hereditary diseases was also carried out on this group. The ABO, Rhesus, MN and Duffy system frequencies varied significantly from the figures obtained for the Greek population. However, there is a characteristic similarity between various gypsy groups studied in other nations and the distribution of polymorphic traits in the Punjab region of India. Cystic fibrosis, renal tubular acidosis, 21-hydroxylase deficiency, Hoty-Oram syndrome and homozygous beta-thalassemia were diagnosed within the gypsy group studied.
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PMID:Genetic structure of the Greek gypsies. 10 65

We describe the implementation of a modified version of the reverse dot blot hybridization technology to detect eight cystic fibrosis mutations. The method is simple, quick, reliable, inexpensive, and nonradioactive and utilizes the sensitivity of the polymerase chain reaction coupled with colored or chemiluminescent substrates for mutation detection. We have used this system in a clinical laboratory to identify the delta F508, G542X, G551D, R553X, 621 + 1G----T, W1282X, N1303K, and 1717G----A mutations. The technique is practical for genotyping individuals at many potential mutation sites, as in cystic fibrosis and beta-thalassemia, in which over 95 mutations can cause disease. This technology appears to be the method of choice for the widespread carrier screening of multiple cystic fibrosis mutations.
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PMID:Detection of multiple cystic fibrosis mutations by reverse dot blot hybridization: a technology for carrier screening. 158 26

In human red cells, Ca is mainly bound to the inner side of the plasma membrane. A smaller part may be present within intracellular Ca storing vesicles, while only a few percent of total red cell Ca is in ionized form. In some hemolytic anemias (sickle cell anemia, beta-thalassemia), an increased number of endocytotic vesicles storing Ca is probably responsible for the elevation of total red cell Ca content. Red cell Ca inward transport, which is partially susceptible to inhibition by Ca entry blockers, has been reported to be enhanced by physiological shear stress and enrichment in membrane cholesterol, as well as in some hemolytic anemias. Normal intracellular ionized Ca levels have been assessed in several diseases where elevated Ca inward transport rates or decreased Ca efflux through the Ca pump (hemolytic anemias, cystic fibrosis, essential hypertension) had been observed previously. Thus, red cell Ca homeostasis is apparently capable of keeping ionized Ca levels within the physiological range of 20-60 nM under most pathological conditions investigated so far. Conceptually, changes in red cell Ca homeostasis (or also in other red cell membrane parameters) may be of pathophysiological importance in two respects: 1) A disturbance may be directly responsible for some of the symptoms associated with a disease. This is the case in sickle cell anemia, where red cell dehydration is possibly caused by transient elevations of intracellular ionized calcium, which may activate K efflux through the Ca-activated K channel. The presence of dehydrated red cells will, in turn, lead to microvascular occlusion, a pathophysiologically important phenomenon in sickle cell anemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium homeostasis of human erythrocytes and its pathophysiological implications. 164 22

Screening for genetic abnormalities is an integral part of obstetrics. Prior to initiating screening, however, several prerequisites must be met: (i) capacity to alter clinical management, (ii) cost effectiveness, (iii) reliable means (usually assays) of assessment, and (iv) capacity to handle problems. In all pregnancies one should determine in systematic fashion whether family history places a pregnant woman at increased risk over the background risk of 2-3% congenital anomalies. All women over age 35 years at delivery should be offered prenatal cytogenetic testing, and women of all ages should be offered maternal serum alpha-fetoprotein screening for neural tube defects. Screening ostensibly normal populations is appropriate in certain ethnic groups to determine heterozygosity for selected disorders: Blacks for sickle-cell anaemia, Mediterranean people for beta-thalassaemia, Southeast Asians and Filipinos for alpha-thalassaemia, Ashkenazi Jews and perhaps French-Canadians for Tay-Sachs disease. Cystic fibrosis screening (delta F508 mutations) is not currently recommended for the general populations, but should be offered to relatives of an individual having delta F508 cystic fibrosis. Irrespective of the extent of screening programmes for Mendelian traits, the mutant allele will remain in the general population because by far the greatest genetic load lies in clinically normal heterozygotes, affected contributing far less to the load despite the obvious clinical effect.
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PMID:Screening for fetal and genetic abnormalities. 172 71

Gene amplification by the polymerase chain reaction (PCR) has been applied to prenatal diagnosis for alpha and beta thalassemias (1 and 5 cases respectively), Hemoglobin (Hb) Lepore/beta thalassemia (1 case) and cystic fibrosis (14 cases). Chorionic villus samples were obtained in the tenth week of pregnancy and DNA analysed in parallel with conventional gene mapping. Direct diagnosis of the common Mediterranean beta-thalassemia mutations (IVS-1-110 and codon 39), Hb Lepore, and the delta F508 mutation causing cystic fibrosis was achieved by hybridization of amplified material with pairs of allele-specific oligonucleotide (ASO) probes or by restriction enzyme digestion of PCR products. Results were confirmed by DNA mapping. Definitive diagnosis or exclusion of an affected fetus was possible in 17 of 21 cases thus examined. PCR reduces the time required for prenatal diagnosis. DNA contamination is a potential source of error.
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PMID:Utility of the polymerase chain reaction (PCR) for prenatal diagnosis of genetic disease. 174 68

The haploid nucleus of a human cell contains 3 X 10(9) base pairs. Organized in linear duplex, this DNA would stretch out to a length of some 90 cm. Thus, organization of chromosomes has been a major subject for pioneer cytogenetists. Long lasting controversies on the strandedness of chromosomes, together with newly developed banding techniques, led us to molecular cytogenetics. Next, the discovery of reverse transcriptase, restriction endonucleases, and other recombinant DNA methods have enabled us to isolate and characterize genes from any organism and to determine the DNA sequences and any encoded protein sequences. These new technologies have already helped us to understand many inherited diseases at a molecular level. In sickle cell anemia, thalassemia and in other mendelian disorders we can know their molecular defects by examining the DNA from peripheral leukocytes, without the need for complex biochemical assays or biopsies. Southern blot analysis using restriction endonuclease and a probe is a basic tool for molecular diagnosis. cDNA or DNA fragments are used as probes. Recently, synthesized oligonucleotide probes are available, if the DNA sequence of a gene is determined. In addition, restriction fragment length polymorphisms (RFLPs), play a very important role in the molecular diagnosis. Linkage analysis using RFLPs linked to the gene locus of a certain disease also permits the detection of the patients and carriers within families with genetic diseases of unknown cause. Starting with the genetic map and physical map, genes for cystic fibrosis and Duchenne muscular dystrophy have recently been isolated and cloned.
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PMID:[Recent advances in human molecular genetics]. 197 24

We have developed a new nonradioactive method for the identification of mutations causing beta-thalassemia and cystic fibrosis. The method is based on the priming of polymerase chain reaction (PCR) by an oligonucleotide complementary to the DNA sequence containing the mutation of interest, which anneals only to the perfectly matched sequence under high stringency conditions. A more upstream oligonucleotide primer is also included in the reaction to discriminate between homozygosity and heterozygosity for a particular mutation and serves as a control for the efficiency of the amplification.
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PMID:Mutant oligonucleotide extension amplification: a nonlabeling polymerase-chain-reaction-based assay for the detection of point mutations. 202 57

In 1989 we are continuing to move gene diagnosis over to the direct detection mode. We have sickle cell anemia, alpha-thalassemia, beta-thalassemia, Duchenne muscular dystrophy, Becker muscular dystrophy and cystic fibrosis moved to direct detection with hemophilia B and alpha-1-antitrypsin deficiency soon to be there. For indirect detection, we still have hemophilia A, and a comment on the genetics of hemophilia A is important. Remember that sickle cell anemia is caused by one mutation, while beta-thalassemia and cystic fibrosis have a finite number of alleles. Duchenne muscular dystrophy results from a different mutation for every affected individual, but most of these are deletions and can be directly detected. Hemophilia A is another X-linked disorder with almost every affected individual having a different mutation. That means that there probably are 100 ways to get beta-thalassemia and about 10,000 ways to get hemophilia A, so we need some really good novel techniques to detect these directly, and we are working hard on such techniques. I would not be surprised if hemophilia A moved into the direct detection category in the next year or so. We need to find the Huntington disease gene, and then it will move into the direct detection column. Neurofibromatosis is still in the indirect detection group but also may move very soon. Polycystic kidney disease is also still in the indirect detection column. This summarizes where prenatal and presymptomatic gene diagnosis stands in late 1989.
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PMID:Current status of prenatal diagnosis by DNA analysis. 209 48

The challenges in the control of genetic disorders will be to provide pediatric surgery, continuous medical or social support, and research. The focus of this report is on the factors influencing the relevance of genetics programs for public health: genetic epidemiology, genetic structure, demographic factors, and the level of development of the country. Approaches for control of genetic diseases must accept that prevention and treatment are usually impossible. The only remaining alternative is avoidance through genetic counseling and genetic counseling and genetic screening neonatally, or before and during pregnancy with ultrasound or alpha fetoprotein serum screening. Some pregnancies at risk may be identified by advanced maternal age distribution and country. There is also the possibility of premarital carrier detection, which has been successful in the identification of thalassemia in Cyprus. Carrier detection can occur both before and during pregnancy for groups at risk for Tay-Sachs disease, sickle cell disease, and thalassemia. In the future, there may be carrier tests available for certain common inherited diseases such as cystic fibrosis. Fetal diagnosis ensures the delivery of a healthy child for some conditions. Thus far amniocentesis, fetal blood sampling, and chorionic villus sampling do not indicate an excessive rate of fetal loss, but laboratory diagnosis is dependent on accuracy of readings. Cytogenetic, biochemical, and DNA methods need improvement. The limitation of fetal diagnosis is that the only avoidance option is abortion. Problems also exist in the delivery of genetic services. Based on existing services in Europe, no more than 20% of the genetic burden is avoided, unless there is good public education an counseling at the community level. Obstetricians and practicing physicians need training in genetic counseling. Professional codes of practice need to be instituted. The effectiveness of control measures is dependent on the strategy adopted and must pertain to the country-specific needs. A monitoring body may be required to ensure fairness, effectiveness, and improvement in service delivery. Appropriate nutritional and public health strategies need to be formed to account for the genetically determined population differences, i.e., lactose intolerance, G6PD deficiencies, or hemoglobin E/Beta thalassemia, for all diseases have a genetic determinant.
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PMID:Problems in the control of genetic disorders. 213 Sep 14

Using the recent developments of molecular biology techniques, our laboratory is offering carrier and prenatal diagnosis for a variety of genetic disorders including cystic fibrosis, phenylketonuria, thalassaemia alpha and beta, sickle cell anaemia, myotonic dystrophy, von Recklinghausen's disease, autosomal polycystic kidney disease, haemophilia A and B, Martin-Bell syndrome (fragile X), Becker and Duchenne muscular dystrophy, etc. It is likely that the rapid advances made in the establishment of the human genetic map will considerably expand the spectrum of diseases for which diagnosis by molecular genetics will become available.
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PMID:[Molecular and diagnostic genetics]. 219 51


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