Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prenatal diagnoses of the genetic disorders alpha, beta thalassemia, HbS, Hb Lepore, hemophilia and cystic fibrosis were sought in 88 cases. Six unsuccessful attempts at diagnosis resulted from DNA polymorphisms which were only 50% informative (four cases) and prenatal diagnoses which had been undertaken before it was known whether DNA polymorphisms in family studies were informative (two cases). The most frequent indications for prenatal diagnosis were the hemoglobinopathies although requests for exclusion of cystic fibrosis formed the majority during 1989. Strong linkage disequilibrium between the cystic fibrosis defect and its associated DNA polymorphisms facilitated detection of this disorder. Late presentations among patients with beta thalassemia and hemophilia and the necessity for more specialised genetic counselling were the commonest problems encountered.
 ...
PMID:Experience of a molecular genetics service in prenatal diagnosis by DNA analysis. 224 30

Clinical chemistry is going through an identity crisis, squeezed between automation (de-skilling) on the service side and molecular genetics in research. Automated routine estimations are now carried out and interpreted by machines; the skilled staff members required are more likely to have degrees in electronics than medicine or biochemistry. The role of molecular genetics is more ambiguous; it is inherently reductionist, in that it attempts to explain most clinical phenomena in terms of DNA sequence alone. This has been remarkably successful for single-gene defects (such as those causing Duchenne muscular dystrophy, hemoglobinopathies, cystic fibrosis, and ataxias) and may well prove equally so for Alzheimer's disease, cancer, heart disease, and schizophrenia. DNA diagnosis is not yet routine, but because of technical advances such as gene amplification ("PCR") and high-sensitivity gene-detection assays, it may soon become so, not only in major centers but also in local pathology laboratories and general practice. Clinical chemists must decide whether they wish to respond to this new and stimulating challenge by retooling and retraining. Should anyone be permitted into clinical chemistry during the 1990s without knowledge of both electronics and molecular genetics? Will there be a clinical chemistry in the twenty-first century other than through molecular genetics? This article is a personal response to these questions.
 ...
PMID:Molecular genetics and the transformation of clinical chemistry. 233 3

New reproductive genetics means recently developed techniques to prevent the birth of children with specific defects or genetic diseases by testing individuals for sickle cell anemia, the thalassemias, Tay-Sachs disease, cystic fibrosis, or Down syndrome. Third World health services have many deficiencies with high maternal mortality rates (30-40 fold higher than in developed countries), the low percentage of births delivered by health personnel, the high rates of low birth weight babies, and high child malnutrition and infant mortality rates. The main issues in women's reproductive health are fertility regulation, abortion, maternal mortality, sexually transmitted diseases, and infertility. As a result of expansion in contraceptive use worldwide, the total fertility rate in developing countries has declined from 6.1 in 1965 to 3.9 in 1990. It is estimated that, worldwide, 36-53 million induced abortions are performed each year, most of them in developing nations. WHO estimates that more than 500,000 women die each year because of complications of pregnancy, most in developing countries. More than 95% of the 13 million estimated deaths of children under 5 years of age have occurred in these countries. Approximately 200 million people carry a potentially pathologic hemoglobinopathy gene, and about 250,000 children are born every year with hemoglobinopathy, most of them in the developing world. Reproductive genetic testing in big cities and in private for-profit ventures cater to the socioeconomic elite. Amniocentesis is often misused for fetal sex determination to abort female fetuses in India. Currently, in Cuba virtually every pregnant woman is tested for sickle cell trait and maternal serum alpha-fetoprotein levels between 15 and 20 weeks of gestation. It is predicted that the judicious use of reproductive genetic testing will be possible when health and quality of life issues are addressed properly.
 ...
PMID:Reproductive health and genetic testing in the Third World. 840

Five different enzymes, carbamyl phosphate synthetase I (CPS I), ornithine transcarbamylase (OTC) argininosuccinate synthetase (AS), argininosuccinate lyase (AL) and arginase (AR) play a role in urea synthesis from ammonium. The structures of cDNA of all these enzymes and those of genome DNA of some enzymes (OTC, AL, AR) have been already clarified, and using of the information, the alleles of each enzyme deficiency have been identified. Alleles are extremely heterogeneous in all enzyme deficiencies, in sharp difference from other inborn errors of metabolism, such as cystic fibrosis and hemoglobinopathies.
 ...
PMID:[Molecular basis of urea cycle disorders]. 846 64

Whole blood collected on filter paper (Guthrie cards) has provided an excellent means for screening inborn errors of metabolism in neonates. Traditional biochemical methods adapted for use with this collection device have proven instrumental in the detection of many congenital defects such as phenylketonuria, galactosemia, hypothyroidism and hemoglobinopathies. The advent of molecular techniques, specifically polymerase chain reaction (PCR), has resulted in unparalleled advances in diagnostic sensitivity. Because of its ability to amplify small quantities of deoxyribonucleic acid (DNA), PCR has proven particularly successful for use with Guthrie card bloodspots in the identification of many genetic disorders including cystic fibrosis, sickle cell anemia and muscular dystrophy. Furthermore, it has been suggested that Guthrie cards represent a vast archive of genomic material yet to be explored. In this article we review our experience using Guthrie card bloodspots for PCR amplification of the cystic fibrosis gene, describe the advantages and limitations of this technology and speculate on future prospects for molecular diagnostics over the next 100 years.
 ...
PMID:Cystic fibrosis: molecular approaches to diagnosis. 984 5

Reverse allele specific oligonucleotide assays provide a robust method for the molecular characterization of high-mutation spectrum disorders. Commercial test have been developed for human leukocyte antigens class I and class II regions of human chromosome 6, the cystic fibrosis transmembrane conductance regulator at 7q31 and strains of human Hepatitis B and C virus. In their most developed form, these assays rely upon highly multiplexed PCR reactions containing biotinylated primers providing a substrate for nonradioactive detection systems. Sophisticated reverse dot-blot technology involves mechanized covalent attachment of activated primary amine-conjugated oligonucleotides to carboxylated nylon membranes or bovine serum albumin. Subsequent to line or dot printing, membranes are stored or sold dry in preparation for hybridization. Circular spots or lines are visualized colorimetrically after hybridization through the use of streptavidin horseradish peroxidase incubation followed by development using tetramethylbenzidine and hydrogen peroxide, or via chemiluminescence after incubation with avidin alkaline phosphatase conjugate and a luminous substrate susceptible to enzyme activation, such as CSPD, followed by exposure to x-ray film. The entire procedure from blood specimen receipt to result usually requires less than 1 day. Because of the simplicity, speed, and generally high sensitivity and specificity, large numbers of individuals can be rapidly screened using this technology. Rapid turnaround is often required in prenatal diagnosis of cystic fibrosis, beta-thalassemia and hemoglobinopathies, giving this technology has special applicability in those genetic diseases. Commercial instruments are available which automate the hybridization and color development. In addition, scanning software can capture the probe reactivity pattern and interpret it in terms of a genotype.
 ...
PMID:Origin and utility of the reverse dot-blot. 1264 92

This study explored the value of informing beta-thalassaemia carriers of the advantages, as well as the disadvantages of carrier status. Twenty-eight carriers of beta-thalassaemia were interviewed immediately after counselling, and again 2 weeks later. Both interviews included administration of a psychological scale (previously used for cystic fibrosis). Immediately after the first interview the intervention group (n = 18) were informed of the protective effect of the beta-thalassaemia trait against malaria and coronary heart disease. The control group (n = 10) was given the same information after the second interview. The effect of giving the positive information was assessed by comparing participants' scores at the first and second interview. Knowledge of carrier status aroused several negative feelings, including shock, sadness, and anger, but little feeling of stigmatization. Two weeks later, negative feelings were unchanged in the control group, but they were reduced in all members of the intervention group. All members of the intervention group considered it important to inform carriers of the positive aspects as well as the risks associated with carrier status. Carriers of recessive disorders with a known heterozygote advantage should be informed of the advantage. This information has now been incorporated into the comprehensive information system for hemoglobin disorders available at http://www.chime.ucl.ac.uk/ApoGI/.
 ...
PMID:Informing carriers of beta-thalassemia: giving the good news. 1534 6

With increasing concerns regarding rapidly expanding health care costs, cost-effectiveness analysis (CEA) provides a methodology to assess whether marginal gains from new technology are worth the increased costs. In the arena of prenatal diagnosis, particular methodological and ethical concerns include whether the effects of such testing on individuals other than the patient are included, how termination of pregnancy is included in the models, redundancy of screening and diagnostic methods, and how screening may reassure or cause anxiety in patients depending on their results. The existing literature has demonstrated cost-effectiveness of screening and diagnosis of neural tube defects, Down syndrome, and cystic fibrosis in the general population. Screening for genetic disorders which have a higher prevalence among particular groups has also been shown to be cost effective, including diseases such as hemoglobinopathies and Tay-Sachs disease. Understanding the methodology and salient issues of CEA is critical for researchers, editors and clinicians to accurately interpret results of the growing body of cost-effectiveness studies in prenatal diagnosis.
 ...
PMID:Cost-effectiveness analysis of prenatal diagnosis: methodological issues and concerns. 1569 15

Epistasis or modifier genes, that is, gene-gene interactions of non-allelic partners, play a major role in susceptibility to common human diseases. This old genetic concept has experienced a major renaissance recently. Interestingly, epistatic genes can make the disease less severe, or make it more severe. Hence, most diseases are of different intensities in different individuals and in different ethnicities. This phenomenon affects sickle-cell anemia carriers and other hemoglobinopathies, systemic lupus erythematosus, cystic fibrosis, complex autoimmune diseases, venous thromboembolism, and many others. It is likely, and fortunate, than 20 years form now, patients entering a medical facility will be subjected to a genomic scanning, including pathogenic genes as well as epistatic genes.
 ...
PMID:Epistasis and the genetics of human diseases. 1599 44

4-Phenylbutyrate (4-PBA) is an oral butyrate derivative that has recently been approved for treatment of urea cycle disorders and is under investigation in clinical trials of cancer, hemoglobinopathies, and cystic fibrosis (CF). We hypothesized that proteome profiling of IB3-1 cystic fibrosis bronchial epithelial cells treated with 4-PBA would identify butyrate-responsive cellular chaperones, protein processing enzymes, and cell trafficking molecules associated with the amelioration of the chloride transport defect in these cells. Protein profiles were analyzed by two-dimensional gel electrophoresis and mass spectrometry. Over a pI range of 4-7 and molecular weight from 20 to 150 kDa a total of 85 differentially expressed proteins were detected. Most of the identified proteins were chaperones, catalytic enzymes, and proteins comprising structural elements, cellular defense, protein biosynthesis, trafficking activity, and ion transport. Subsets of these proteins were confirmed by immunoblot analysis. These data represent a first-draft of the pharmacoproteomics map of 4-PBA treated cystic fibrosis bronchial epithelial cells.
 ...
PMID:Pharmacoproteomics of 4-phenylbutyrate-treated IB3-1 cystic fibrosis bronchial epithelial cells. 1651 71


1 2 3 4 Next >>