Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A search of the Human Genome Sciences database of expressed sequence-tagged DNA fragments, for sequences containing homology to known yeast DNA recombination and repair genes, yielded a cDNA fragment with high homology to RAD54. Here we describe the complete cDNA sequence and the characterization of the genomic locus coding for the human homologue of the yeast RAD54 gene (hRAD54). The yeast RAD54 belongs to the RAD52 epistasis group and appears to be involved in both DNA recombination and repair. The hRAD54 gene maps to chromosome 1p32 in a region of frequent loss of heterozygosity in breast tumors and encodes a protein of M(r) 93,000 that displays 52% identity to the yeast RAD54 protein. The hRAD54 protein sequence additionally contains all seven of the consensus segments of a superfamily of proteins with presumed or proven DNA helicase activity. Mutations in genes with consensus helicase homology have been found in cancer-prone syndromes such as xeroderma pigmentosum and Bloom syndrome as well as Werner's syndrome, in which patients age prematurely, and the X-linked mental retardation with alpha-thalassemia syndrome, ATR-X. We have examined the hRAD54 gene in several breast tumors and breast tumor cell lines and, although the gene region appears to be deleted in several tumors, at present we have found no coding sequence mutations.
Cancer Res 1997 Jun 15
PMID:Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors. 919 13

Sixty-four children with malignant brain tumours diagnosed at less than 3 years of age were reported to the Finnish Cancer Registry from 1975 to 1993. The survival rate has improved significantly: the 5-year survival rate was 26% for all children, 13% for children diagnosed during 1975-85 (n = 30) and 40% for those diagnosed during 1986-93 (n = 34). Of the surviving children in 1986-93, 43% were categorized in Bloom's group I or II and could lead active lives without major disabilities. The remaining children had severe neurologic late complications, such as hemiplegia, intractable seizures, and mental retardation.
 ...
PMID:Improving outcome of malignant brain tumours in very young children: a population-based study in Finland during 1975-93. 924 Aug 80

Down syndrome (DS) is associated with mental retardation, immune disorders and congenital heart diseases. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic phenotypic features may be caused by the presence of the band 21q22, called the "Down syndrome region". Many proteins important for the immune and nervous systems as CuZn-superoxide dismutase (SOD-1), CD18-beta chain of LFA-1, interferon receptor, APP-amyloid precursor protein, protein S-100 beta are coded by chromosome 21. Overexpression of these molecules may contribute to the thymic derangement that results in anomalous maturation leading to functionally impaired T cells. Many factors have been shown to contribute to the immune deficiency which results in high susceptibility to infections, high rate of malignancies, and autoimmune phenomena in persons with DS. The main disorders in the immune system include thymus abnormalities, changes in cell-mediated immunity, phagocytosis, antibodies-mediated immunity and a high prevalence of autoantibodies in persons with DS. Furthermore, the duplication of chromosome 21 genes may generate most of the pathological changes in the central nervous system. There is an increased prevalence of seizure disorders. Such widespread alterations in the cortical areas seem to account for specific impairments observed in short-term and long-term memory, language skills, and cognitive and learning processes. If all principles of optimal health care and adequate education were followed without exception for persons with DS, then the quality of their life could be improved significantly and they would be able to become productive citizens in the society. (Tab. 5, Fig. 3, Ref. 42.)
 ...
PMID:[Down's syndrome--effect of increased gene expression in chromosome 21 on the function of the immune and nervous system]. 926 31

Cohen syndrome is an autosomal recessive disorder characterized by mental retardation, microcephalia and typical craniofacial features, myopia and chorioretinal dystrophy. As some patients were reported to have leucopenia, we collected the haematological data of 26 Finnish Cohen patients. They all had experienced periods of isolated granulocytopenia from an early age. Granulocytopenia was mild to moderate, non-cyclic and never fatal. Most patients suffered from prolonged or repeated gingival or skin infections. We restudied 16 patients. Bone marrow examination revealed in all patients a normo- or hypercellular marrow, with a left-shifted granulopoiesis in 8/16 patients. The response to adrenaline stimulation was subnormal in 12/14 and to hydrocortisone in 8/16 patients, but administration of rhG-CSF caused granulocytosis in the three patients studied. No bone marrow malignancies were seen.
 ...
PMID:Granulocytopenia in Cohen syndrome. 926 25

The functionality of the p53-mediated pathway, activated in response to DNA damage, has been assessed in primary fibroblast cell cultures and Epstein-Barr virus-transformed lymphoblastoid cell lines derived from Nijmegen breakage syndrome (NBS) patients. This autosomal recessive disease is characterized by microcephaly, growth and mental retardation, chromosomal instability, radiosensitivity, and high cancer incidence. The recent mapping of the NBS gene to chromosome 8q21 demonstrates that NBS is genetically distinct from ataxia telangiectasia (AT). Changes in p53 protein levels were significantly reduced and delayed in all the NBS fibroblast cell cultures and lymphoblastoid cell lines examined compared to normal cultures over a 4-h period postirradiation (5 Gy). The transcriptional activation of p21(WAF1/CIP1) mRNA was also lower in 12 NBS fibroblast cultures examined. In agreement with an abrogated p53 function, NBS cells exposed to ionizing radiation show an abnormal cell cycle arrest at G1-S and a prolonged accumulation of cells in the G2 phase. In contrast, exposure to the alkylating agent methyl methanesulfonate results in similar increases of p53 and p21(WAF1/CIP1) mRNA in both cell types. The ATM gene transcript was found to be expressed at similar levels in NBS and normal cells, whereas it was strongly reduced in the AT homozygote cells examined. These results suggest that the ATM gene product cannot substitute for that of the NBS gene in the signaling of cellular damage produced by ionizing radiation and that both are involved in the activation of p53. The suboptimal p53-mediated response could contribute to the high cancer risk and radiosensitivity seen in NBS patients.
 ...
PMID:Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation. 927 79

FMR2 is the gene associated with FRAXE mental retardation. It is expressed as an 8.7-kb transcript in placenta and adult brain. A fetal-specific FMR2 transcript of approximately 12 kb was detected in fetal brain and at a lower level in fetal lung and kidney. FMR2 is a large gene composed of 22 exons spanning at least 500 kb on Xq28. Alternative splicing involving exons 2, 3, 5, 7, and 21 was not tissue specific as tested on mRNA from human fetal and infant brain. FMR2 is translated into a 1311-amino-acid nuclear protein with putative transcription transactivation potential. Subcellular localization studies with green fluorescent protein as a reporter show that both nuclear addresses found in the FMR2 sequence are functional and direct the FMR2 protein into the nucleus. FMR2 together with AF4 and LAF4 forms a new family of nuclear proteins with DNA-binding capacity and transcription transactivation potential. BLAST searches of the dbEST database revealed the presence of at least two other groups of nonoverlapping ESTs showing high similarity to the FMR2-related family of proteins. One of them, represented by the EST W26686, maps to chromosome 5q31. Amino acid similarity among the proteins encoded by members of the gene family is high in the NH2 terminus, low in the middle, and high again in the COOH end. Available information from members of the family shows that genomic organization is conserved. This FMR2-related gene family encodes nuclear proteins with involvement in mental retardation (FMR2), cancer (AF4), and lymphocyte differentiation (LAF4) or with unknown function (EST W26686 and/or AA025630).
 ...
PMID:Gene structure and subcellular localization of FMR2, a member of a new family of putative transcription activators. 929 37

To optimize the efficacy of radiotherapy for cancer patients who are pregnant, the following factors must be considered: the potential effects of the therapy on fetuses and neonates, the stage and prognosis of the mother's disease, and the possible risks to the patient of restricting cancer treatment. Malformations and mental retardation are the most serious consequences of fetal exposure to radiation that are observed after birth. The sensitivity to radiation is high from 2 to 8 weeks after conception for malformations and from 8 to 25 weeks (particularly up to week 15) for mental retardation; the risk of mental retardation declines rapidly after the 25th week of gestation. When a pregnant patient requires radiation therapy, the physician should consider fetal sensitivity to radiation in light of gestational age and the expected dose of radiation and should then calculate the risk to the fetus versus the benefits to the mother. The risk is negligible if fetal exposure does not exceed 0.1 Gy, preferably remaining below 0.05 Gy, during gestation. Furthermore, it is safest to administer radiotherapy during or after the 25th week of gestation.
 ...
PMID:Radiotherapy during pregnancy: effects on fetuses and neonates. 937 20

The embryonal stage in mammalians is characterized by a quick proliferation and differentiation of cells. The special features of this stage of development in all living beings is therefore an increased sensitivity for the exposure with ionizing radiation. Radiation exposure during the prenatal development can therefore lead to various impairments, which can be short-termed or long-termed, showing effects even in the postnatal period. The pattern of radiation induced effects is dependent upon the radiation dose on the one hand and upon the stage of fetal development when radiation exposure occurs on the other hand. Radiation induced effects can be growth retardation, malformations, functional impairments or death as well as increased occurrence of cancer and leukemia during childhood. The main effects of a radiation exposure in the fetal period are: 1) lethal effects for the embryo, 2) malformations and changes in growth or other functional changes, 3) mental retardation, 4) induction of malignomas including leukemia. Lethal effects can be induced experimentally in animals by relatively low radiation doses of 10 cGy, administered before or immediately after the implantation of the embryo. Malformations can be induced if the exposure occurs during the period of organogenesis especially if the radiation exposure occurs during the active stage of increased cell formation and cell differentiation of a specific organ. For many types of effects of ionizing radiation especially for the death of the embryo or fetus and for macroscopic anatomical malformation a dose-effect relationship with certain threshold doses can be supposed. This threshold dose is not smaller than 5 cGy if the exposure results from a low level radiation with low LET> Radiation exposure at the end of the organogenesis and during the following fetal period can induce growth retardation and functional disturbances, which are characterized by abnormalities in the postnatal period. Of special importance are the abnormalities of the CNS, like mental retardation particularly if the radiation exposure occurred during the interval between the 8th and 15th week of pregnancy. During that time period cell formation for the development of the frontal brain occurs. The induction of this type of abnormalities as well as of other malformations is due to non stochastic effects. A threshold dose of 5 cGy ist discussed. The induction of malignancies and leukemia as a consequence of a radiation exposure in the prenatal period is to be seen as a deterministic (non stochastic) radiation effect. The sensitivity of the fetus for these effects ist 2 to 3 times higher than that of adults.
 ...
PMID:[Exposure to radioactive iodine in pregnancy: significance for mother and child]. 944 52

A cytogenetically visible interstitial deletion of chromosome band 10q23 was found in a 6-year-old boy with mental retardation, dysmorphic features, and juvenile polyposis coli. In order to map this patient's deletion physically, we performed fluorescence in situ hybridization by using yeast artificial chromosomes (YACs) in the vicinity of the deletion. Five YACs that span an 11-15 cM region within the deletion were identified. This patient's deletion contains the putative locus for Cowden syndrome and a recently discovered candidate tumor suppressor gene (MMAC1 or PTEN) that has been implicated in the progression of a variety of human malignancies. Furthermore, the deletion is near and possibly overlaps a locus associated with juvenile polyposis. The findings in this patient with a constitutional 10q23 deletion raise the issue of whether there are separate genes in this region that are involved in Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, juvenile polyposis, and tumor progression, or whether all of these entities could be due to a single gene.
Genes Chromosomes Cancer 1998 Feb
PMID:Deletion 10q23.2-q23.33 in a patient with gastrointestinal juvenile polyposis and other features of a Cowden-like syndrome. 949 22

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity, and cancer predisposition. A-T cells are sensitive to ionizing radiation and radiomimetic chemicals and fail to activate cell-cycle checkpoints after treatment with these agents. The responsible gene, ATM, encodes a large protein kinase with a phosphatidylinositol 3-kinase-like domain. The typical A-T phenotype is caused, in most cases, by null ATM alleles that truncate or severely destabilize the ATM protein. Rare patients with milder manifestations of the clinical or cellular characteristics of the disease have been reported and have been designated "A-T variants." A special variant form of A-T is A-TFresno, which combines a typical A-T phenotype with microcephaly and mental retardation. The possible association of these syndromes with ATM is both important for understanding their molecular basis and essential for counseling and diagnostic purposes. We quantified ATM-protein levels in six A-T variants, and we searched their ATM genes for mutations. Cell lines from these patients exhibited considerable variability in radiosensitivity while showing the typical radioresistant DNA synthesis of A-T cells. Unlike classical A-T patients, these patients exhibited 1%-17% of the normal level of ATM. The underlying ATM genotypes were either homozygous for mutations expected to produce mild phenotypes or compound heterozygotes for a mild and a severe mutation. An A-TFresno cell line was found devoid of the ATM protein and homozygous for a severe ATM mutation. We conclude that certain "A-T variant" phenotypes represent ATM mutations, including some of those without telangiectasia. Our findings extend the range of phenotypes associated with ATM mutations.
 ...
PMID:Genotype-phenotype relationships in ataxia-telangiectasia and variants. 949 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>