Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rare association of alpha thalassaemia and mental retardation has been described previously. Molecular studies of the alpha globin cluster in these cases have been heterogeneous, with some patients having large deletions while in others the alpha globin complex appears to be intact (non-deletional). The non-deletional cases form a distinct group whose features include severe mental retardation, haematological changes of haemoglobin H (Hb H) disease, developmental defects, and unusual patterns of inheritance. To date, five cases have been described with non-deletional alpha thalassaemia-mental retardation. We present here a further example of a young male of Northern European origin who appears to have the non-deletional form of the disease. Clinical features included severe mental retardation, Hb H disease, and developmental defects similar to those reported previously. DNA mapping, including pulsed field electrophoresis, showed no evidence of deletions within the alpha globin cluster. Karyotypic analysis indicated an increase in random breakage, which has been observed previously in one case of deletional alpha thalassaemia-mental retardation. Profuse Hb H bodies and Hb H on electrophoresis were consistent with Hb H disease. However, the latter was present at a relatively low level (1.6%) and, as well, the mean corpuscular volume (82.8 fl) and mean corpuscular haemoglobin (26.4 pg) were surprisingly high. Our findings are compared to other cases described with the non-deletional Hb H-mental retardation syndrome.
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PMID:Occurrence of the alpha thalassaemia-mental retardation syndrome (non-deletional type) in an Australian male. 223 51

Recent work in the alpha thalassaemia field has started to provide some indication of the mechanisms involved in the very high frequency of the different forms of alpha thalassaemia among the populations of tropical countries, and, at the same time, is starting to define at least some of the mechanisms for its remarkable phenotypic heterogeneity. These diseases continue to provide extremely valuable models for the better understanding of the regulation of the alpha globin genes, and for human molecular pathology in general. The much less common disorders, ATR-16 and ATR-X are also providing valuable information about the spectrum of molecular lesions associated with different forms of mental retardation and about the molecular mechanisms involved in their varying phenotypes.
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PMID:The alpha thalassaemias. 1902 Aug 5

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X syndrome, OMIM #301040) is one of the syndromes associated with abnormal epigenetic gene regulation, including ICF(DNMT3B), Rett (MECP2), Rubinstein-Taybi (CBP), Coffin-Lowry (RSK2), and Sotos (NSD1) syndromes. It is a syndromic form of X-linked mental retardation, which affects males and is characterized by profound mental retardation, mild HbH disease (alpha-thalassemia), facial dysmorphism, skeletal abnormalities, and autistic behavior. ATR-X syndrome is caused by a mutation in the ATRX gene on the X chromosome (Xq13), which encodes ATRX protein, belonging to the SNF2 family of chromatin-remodeling proteins. The protein has two functionally important domains: an ADD (ATRX-DNMT3-DNMT3L) domain at the N-terminus, and chromatin-remodeling domain in the C-terminal half, where the ATRX gene mutations of most ATR-X patients reside. Perturbation in DNA methylation in the rDNA genes was repored in ATR-X patients, and ATRX protein is presumed to be involved in the establishment and maintenance of DNA methylation. Based on its various clinical phenotypes, the expressions of many genes, including alpha globin genes, seem to be abnormally regulated in ATR-X patients. However, the precise mechanism involving ATRX protein remains to be elucidated. Epigenetics can link environmental and genetic causes of many pathological conditions. The genes, which are abnormally regulated by a perturbed epigenetic mechanism, are, in themselves, structurally normal, and the elucidation of their mechanism may lead to the development of appropriate therapy.
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PMID:[X-linked alpha-thalassemia/mental retardation syndrome]. 1948 41