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)

Skeletal or cardiac muscle fibers can be separated by brief (3--5 second) dissociation of formalin-fixed pieces with a Willems Polytron (Brinkmann Instrument Co.). Such separated fibers are useful for demonstration of abnormal accumulations of lipids, carbohydrates, proteins and minerals in metabolic diseases. Staining techniques for demonstration of various stored materials include: 1) toluidine blue at pH 2.8 for acid mucopolysaccharide in skeletal muscle fibers in Pompe's glycogenesis 2, 2) one-step trichrome stain for nemaline myopathy and for abnormal mitochondria in X-linked infantile cardiomyopathy, 3) periodic acid-methenamine silver stain for glycolipid-containing lysosomes in I-cell disease (mucolipidosis 2), 4) Sudan black B stain for lipid in skeletal muscle fibers in Reye's syndrome, infantile lactic acidosis, Leigh's infantile subacute necrotizing encephalopathy and Jansky-Bielschowsky late infantile ceroid lipofuscinosis, 5) iron stain for iron in cardiac and skeletal muscle fibers in thalassemia with advanced hemosiderosis, and 6) autofluorescence for "ceroid" in skeletal muscle fibers in Jansky-Bielschowsky disease.
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PMID:Histochemical methods for dissociated muscle fibers. 9 Apr 4

We have examined seven pedigrees that include individuals with a recently described X-linked form of severe mental retardation associated with alpha-thalassemia (ATR-X syndrome). Using hematologic and molecular approaches, we have shown that intellectually normal female carriers of this syndrome may be identified by the presence of rare cells containing HbH inclusions in their peripheral blood and by an extremely skewed pattern of X inactivation seen in cells from a variety of tissues. Linkage analysis has localized the ATR-X locus to an interval of approximately 11 cM between the loci DXS106 and DXYS1X (Xq12-q21.31), with a peak LOD score of 5.4 (recombination fraction of 0) at DXS72. These findings provide the basis for genetic counseling, assessment of carrier risk, and prenatal diagnosis of the ATR-X syndrome. Furthermore, they represent an important step in developing strategies to understand how the mutant ATR-X allele causes mental handicap, dysmorphism, and down-regulation of the alpha-globin genes.
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PMID:X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis. 141 55

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

Contrary to earlier reports from Asia, trisomy 21 is common in Burma and other chromosome abnormalities are found. A variety of dominant, recessive and X-linked genetic disorders occur. Twins are found in 1% of births and MZ and DZ twins are equally common. Thalassaemia and meningomyelocele are relatively common while congenital dislocation of the hip and phenylketonuria are very rare. The intensity of inbreeding had been measured by survey and found to be F = 0.0005 in Rangoon and F = 0.0015 in villages around Hlegu.
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PMID:Human genetics in Burma. 646 Jun 83

At this time a rather large number of congenital abnormalities still occur. About 2-3% of pregnancies will result in children with major congenital abnormalities that cannot be detected prenatally. Yet, with the availability of prenatal diagnosis for an ever increasing number of genetic problems and, more recently, for developmental problems as well, a new option was offered to couples at risk when they took the risk of pregnancy: finding out whether the fetus was abnormal. An early argument regarding the ethics of this option was formulated by Dan Callahan, director of the Hastings Institute for Ethics, Society and the Life Sciences, when he indicated the need to be careful about the term "option." A need exists to be careful about societal pressures in favor of the new medical options--on, for example, a pregnant woman who is over 35 and does not get a prenatal diagnosis; or on a woman carrying a Down's syndrome child identified by prenatal diagnosis not to have an abortion. This was the 1st specter raised when prenatal diagnosis was introduced. The most common indication for amniocentesis is the risk of chromosomal abnormalities. The risk of discovering a chromosomal abnormality by amniocentesis is about double the risk at birth because a number of chromosomally abnormal fetuses are lost late in the 2nd trimester by spontaneous abortion. The age cutoff at 35 raises an immediate ethical question: since the total number of births to women over age 35 seems to be increasing, and at the same time a greater and greater percentage of children with Down's syndrome are born to women under age 35, the question arises as to whether amniocentesis should be done on all pregnancies, and whether all births with Down's syndrome should be selectively aborted or avoided. Amniocentesis in all pregnancies is impractical at this time from the technological and the cost perspective, but the ethical question should be raised. Among the X-linked disorders, 1 group cannot be specifically diagnosed in utero by prenatal diagnosis. If a woman is known to be a carrier, her daughters won't have the disease, but half of them will be carriers. Regarding sex preference as a reason for amniocentesis, all the geneticist can and should do is provide a couple with a base of knowledge and understanding of the options available to them and the outcome of each option. X-linked disorders such as hemophilia and Lesch-Nyhan syndrome and the autosomal recessive biochemical disorders or inborn errors of metabolism such as Tay-Sachs disease and over 100 others can now be diagnosed prenatally. In the vast majority of cases, amniocentesis is performed because the parents already have an abnormal child. Screening programs for Tay-Sachs disease, for sickle cell anemia, and for thalassemia also detect couples at risk. A variety of tools other than amniocentesis are now available for prenatal diagnosis. Much work is being conducted in the prenatal diagnosis of sickle cell anemia and thalassemia.
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PMID:Genetics, amniocentesis, and abortion. 660 72

Fetal haemoglobin (Hb F) levels shows significant variations in health and disease states. In this study we investigated Hb F level in 75 cord bloods, 1266 healthy individuals, 1582 Hb S heterozygotes, 464 sickle cell anaemia, 93 Hb S/beta(0) -thalassaemia and 65 beta-thalassemia major patients. The age range of the study groups varied from newborn to over 60 years of age. Hb F level was measured by an alkali denaturation procedure and by radial immunodiffusion. The ratio of the level of G gamma-globin chains to the level of A gamma-globin chains (G gamma/A gamma) was determined in the patients group by high performance liquid chromatography. The Hb F level was significantly higher in the sickle cell anaemia and beta-thalassemia major patients compared to the Hb S heterozygotes and the normal individuals. Within each group Hb F level was higher in the female population compared to the age-matched male groups. This difference was statistically significant (P < 0.05) in the sickle cell disease patients and beta-thalassemia major patients but not in the normal individuals. After the age of 30 years, the difference in the value of Hb F in the male and female population become more apparent (P < 0.05) in the sickle cell disease and beta-thalassaemia major patients. No statistically significant sex differences were found in the G gamma/A gamma ratio in the patient groups, and the range of G gamma/A gamma ratio in the patients groups were similar to those in the control group. The results showed that age, sex and genetic disorders of haemoglobin are factors that affect Hb F level and indicate the possible involvement of an X-linked factor in control of Hb F production.
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PMID:Fetal haemoglobin level--effect of gender, age and haemoglobin disorders. 753 Aug 9

The ATR-X syndrome is an X-linked disorder comprising severe psychomotor retardation, characteristic facial features, genital abnormalities, and alpha-thalassemia. We have shown that ATR-X results from diverse mutations of XH2, a member of a subgroup of the helicase superfamily that includes proteins involved in a wide range of cellular functions, including DNA recombination and repair (RAD16, RAD54, and ERCC6) and regulation of transcription (SW12/SNF2, MOT1, and brahma). The complex ATR-X phenotype suggests that XH2, when mutated, down-regulates expression of several genes, including the alpha-globin genes, indicating that it could be a global transcriptional regulator. In addition to its role in the ATR-X syndrome, XH2 may be a good candidate for other forms of X-linked mental retardation mapping to Xq13.
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PMID:Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). 769 14

Genital abnormalities have been noted in several patients with the X-linked form of alpha-thalassemia and mental retardation syndrome (ATR-X). The initial clinical report of the condition documented a phenotypic female with 46,XY karyotype. To this we now add 2 further siblings with abnormalities of the external genitalia, manifesting as male pseudohermaphroditism.
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PMID:Male pseudohermaphroditism in sibs with the alpha-thalassemia/mental retardation (ATR-X) syndrome. 772 24

The hallmarks of the X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome are severe psychomotor retardation, minor facial anomalies, genital abnormalities, and an unusual form of alpha-thalassemia. The demonstration of HbH inclusions in red blood cells after incubation with brilliant cresyl blue confirms the diagnosis. We describe 15 previously unreported cases and analyse the phenotypic and hematologic findings in these subjects and compare them with previously published cases. This study demonstrates the consistency of the main characteristics of this syndrome and extends the phenotype. Developmental changes in phenotype, in particular the coarsening of the facial appearance, are illustrated. The hematologic findings are shown to vary widely; in some cases the manifestation of alpha-thalassemia may be subtle and missed without repeated examination.
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PMID:Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental retardation syndrome (ATR-X). 772 25

Linkage analysis was performed in a three generation family with three males affected by the recently delineated X-linked form of alpha-thalassemia/mental retardation syndrome (ATR-X). Results are in agreement with the linkage study reported by Gibbons et al in 1992 and further confirm that the ATR-X gene is located in proximal Xq. Positive LOD scores were obtained for several markers situated in the pericentromeric region. A maximum LOD score of 2.09 at a recombination fraction of 0 was obtained for DXS453 located at the boundary q12-q13.1. The nearest flanking loci demonstrating recombination with the disease locus were AR at Xq11.2-q12 on the centromeric side and DXS72 at Xq21.1 on the telomeric side. Consequently the authors were able to reduce the previously defined candidate region for the gene location. Their results are compatible with a distal boundary at Xq21.1 instead of q21.31.
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PMID:X-linked alpha-thalassemia/mental retardation syndrome. Linkage analysis in a new family further supports localization in proximal Xq. 816 23


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