Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gene probes can now be used to detect a variety of mutations that produce single-gene disorders. In present clinical practice, restriction endonuclease analysis is used for the prenatal diagnosis of sickle cell anemia, alpha-thalassemia, and beta-thalassemia. Direct detection of the mutation is possible in alpha-thalassemia, where a deletion has usually occurred, and in sickle cell anemia, where the mutation alters the recognition sequence of the restriction endonuclease, Mst II. Indirect detection of beta-thalassemia is based on using normal variations in DNA (DNA polymorphisms) to track normal and affected beta-globin genes in families. This latter kind of analysis is also useful in detecting the phenylalanine hydroxylase genes affected in phenylketonuria and will often be used in disorders where the mutations are unknown. In cases where the mutation is known, direct analysis by use of oligonucleotide probes is a new and important advance. An example of this type of gene detection in a family with classical hemophilia is presented. In addition, with chorion villus biopsy, detection of these inherited diseases is feasible by the 12th week of pregnancy.
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PMID:Gene probes: application to prenatal and postnatal diagnosis of genetic disease. 299 40

Since the early descriptions of sickle cell anemia, it has been clear that genotype at a single locus rarely completely predicts phenotype. This paper reviews explanations for phenotypic variability in some monogenic diseases. In cystic fibrosis, there is strong correlation between genotype and pancreatic phenotype but only weak association with respiratory phenotype, possibly due to differential inheritance of alleles at loci controlling susceptibility to respiratory infection. In addition, disease mutations have been shown to have more or less severe effect, depending on other variation within the cystic fibrosis gene. In phenylketonuria, genotype at the phenylalanine hydroxylase locus appears to explain the biochemical phenotype, but not the intellectual status. There may be genetically determined variation in flux through the minor metabolic pathways for phenylalanine, influencing levels of alternative metabolites involved in mental development. Phenotypic discordance in sickle cell anemia and beta-thalassemia has been associated with the co-inheritance of genes for hereditary persistence of fetal hemoglobin. A mouse locus has been identified that influences tumour number in mice with the multiple intestinal neoplasia gene. Understanding of the genetic interactions that determine phenotype in apparently monogenic diseases should lead to clarification of the role of different genes in polygenic diseases with complex inheritance patterns, as well as enhancing the ability to predict the outcome of a disease mutation.
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PMID:Relationship between genotype and phenotype in monogenic diseases: relevance to polygenic diseases. 872 77

With improvements in early diagnosis and management of genetic diseases, more women with genetic disorders are reaching reproductive age and becoming pregnant. While pregnancy can have a significant impact on a woman's health when there is an underlying genetic disorder, there can also be fetal effects, including embryopathy, fetal growth restriction, and brain injury. Some maternal genetic disorders are associated with adverse perinatal outcomes, including a high risk of perinatal loss and preterm birth. In this article, we review several maternal genetic disorders associated with fetal risk that are important for clinicians and patients to understand and manage appropriately. These include phenylalanine hydroxylase (PAH) deficiency and other inborn errors of metabolism, tuberous sclerosis complex, myotonic dystrophy, cystic fibrosis, Turner syndrome, sickle cell disease, and connective tissue disorders.
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PMID:Maternal genetic disorders and fetal development. 3201 Sep 84