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)

Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate 11p13 Wilms' tumor gene, WT1, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilm's tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome 11 allele encompassing the WT1 gene. Analysis of the remaining WT1 allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WT1 polypeptide as a transcriptional regulator.
Genes Chromosomes Cancer 1993 Jul
PMID:Homozygous inactivation of WT1 in a Wilms' tumor associated with the WAGR syndrome. 768 65

The combined use of qualitative and quantitative analysis of 11p13 polymorphic markers together with chromosomal in situ suppression hybridization (CISS) with biotin labeled probes mapping to 11p allowed us to characterize a complex rearrangement segregating in a family. We detected a pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in the family: an insertion of brand 11p13-p14 carrying the genes for predisposition to Wilms' tumor, WT1, and for aniridia, AN2, into the long arm of chromosome 11 in 11q13-q14. Asymptomatic balanced carriers were observed over three generations. Classical cytogenetics had failed to detect this anomaly in the balanced carriers, who were first considered to be somatic mosaics for del(11)(p13). Two of these women gave birth to children carrying a deleted chromosome 11, most likely resulting from the loss of the 11p13 band inserted in 11q. Although in both cases the deletion encompassed exactly the same maternally inherited markers, there was a wide variation in clinical expression. One child, with the karyotype 46,XY, del(11)(p13p14), presented the full-blown WAGR syndrome with aniridia, mental retardation, Wilms' tumor, and pseudohermaphroditism, but also had proteinuria and glomerular sclerosis reminiscent of Drash syndrome. In contrast, the other one, a girl with the karyotype 46,XX,del(11)(p13), only had aniridia. Although a specific set of mutational sites has been observed in Drash patients, these findings suggest that the loss of one copy of the WT1 gene can result in similar genital and kidney abnormalities.
Genes Chromosomes Cancer 1993 May
PMID:Pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in a family. 768 57

Approximately 4000 women per year in the United States require radiotherapy during pregnancy. This report presents data and techniques that allow the medical physicist to estimate the radiation dose the fetus will receive and to reduce this dose with appropriate shielding. Out-of-beam data are presented for a variety of photon beams, including cobalt-60 gamma rays and x rays from 4 to 18 MV. Designs for simple and inexpensive to more complex and expensive types of shielding equipment are described. Clinical examples show that proper shielding can reduce the radiation dose to the fetus by 50%. In addition, a review of the biological aspects of irradiation enables estimates of the risks of lethality, growth retardation, mental retardation, malformation, sterility, cancer induction, and genetic defects to the fetus.
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PMID:Fetal dose from radiotherapy with photon beams: report of AAPM Radiation Therapy Committee Task Group No. 36. 771 71

The Wilms tumour (WT1) gene was first localized through its deletion in individuals with the WAGR syndrome (Wilms tumour, aniridia, genitourinary abnormalities and mental retardation). Such individuals have a 30-50% lifetime risk of developing Wilms tumour and carry constitutional interstitial deletions of chromosome 11p13, including the WT1 gene. Second primary tumours occurring in such individuals might also be related to their genetic predisposition to cancer, as shown for hereditary retinoblastoma. We have found a mutation in the zinc finger region of the remaining WT1 allele in a case of acute myeloid leukaemia developing in a Wilms tumour survivor with the WAGR syndrome. This mutation would be predicted to disrupt DNA binding by this developmentally regulated transcription factor. This finding implicates the WT1 gene in the regulation of myelopoiesis and suggests that WT1 mutations may be found in some sporadic leukaemias.
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PMID:The Wilms tumour (WT1) gene is mutated in a secondary leukaemia in a WAGR patient. 783 22

The health effects of atomic bomb radiation have been studied by the Atomic Bomb Casualty Commission (ABCC) and its successor, the Radiation Effects Research Foundation (RERF) based on a fixed population of atomic bomb survivors in Hiroshima and Nagasaki which had been established in 1950. The results obtained to the present can be classified into the following three categories: (1) The effects for which a strong association with atomic bomb radiation has been found include malignant neoplasms, cataracts, chromosomal aberrations, small head size and mental retardation among the in utero exposed. (2) A weak association has been found in the several sites of cancers, some non-cancer mortalities and immunological abnormalities. (3) No association has been observed in some types of leukemia, osteosarcoma, accelerated aging, sterility and hereditary effects.
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PMID:[Health effects of atomic bomb radiation]. 817 38

The sun-sensitive, cancer-prone genetic disorder xeroderma pigmentosum (XP) is associated in most cases with a defect in the ability to carry out excision repair of UV damage. Seven genetically distinct complementation groups (i.e., A-G) have been identified. A large proportion of patients with the unrelated disorder trichothiodystrophy (TTD), which is characterized by hair-shaft abnormalities, as well as by physical and mental retardation, are also deficient in excision repair of UV damage. In most of these cases the repair deficiency is in the same complementation group as is XP group D. We report here on cells from a patient, TTD1BR, in which the repair defect complements all known XP groups (including XP-D). Furthermore, microinjection of various cloned human repair genes fails to correct the repair defect in this cell strain. The defect in TTD1BR cells is therefore in a new gene involved in excision repair in human cells. The finding of a second DNA repair gene that is associated with the clinical features of TTD argues strongly for an involvement of repair proteins in hair-shaft development.
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PMID:A new nucleotide-excision-repair gene associated with the disorder trichothiodystrophy. 821 12

Six of 39 sporadic Wilms tumors had gross homozygous or hemizygous WT1 and WIT1 deletions. Two Wilms tumor-aniridia-genitourinary abnormalities-mental retardation syndrome patients had total hemizygous WT1 and WIT1 deletions in both constitutional and nonsporadic type tumor cells. Four of the 8 tumors with WT1 and WIT1 deletions showed loss of constitutional heterozygosity (LOH) for markers limited to the 11p13 region. Seven of 19 Wilms tumors with neither WT1 nor WIT1 deletions also had LOH on 11p; 4 in the 11p15-11p13 region, one in the 11p15 and possibly also 11p13 regions, and two solely in the 11p15 region. Thus, 15 of the 41 Wilms tumors (37%) had WT1 and WIT1 deletions or LOH on 11p, and only 2 of the 27 tumors whose nonneoplastic normal tissues were available for study showed LOH limited to the 11p15 region. None of the 7 non-Wilms childhood renal tumors showed WT1 or WIT1 deletions, or LOH on 11p. These data suggest that Japanese Wilms tumors may be characterized by a higher incidence of the gross WT1 deletion and a lower incidence of LOH limited to the 11p15 region than the Caucasian counterparts. These molecular-genetic features may be contributing to the lower incidence of Wilms tumors in Japanese children than in Caucasian ones.
Jpn J Cancer Res 1993 Jun
PMID:Deletion of WT1 and WIT1 genes and loss of heterozygosity on chromosome 11p in Wilms tumors in Japan. 839 32

We report a 48-year-old Japanese man suffering from xeroderma pigmentosum associated with mental retardation, cerebral atrophy and cerebellar ataxia. Cultured fibroblasts from an unexposed area of skin had reduced DNA repair capacity after UV irradiation, with higher sensitivity to UV than normal cells in colony-forming ability and host cell reactivation using herpes simplex virus. Genetic complementation tests by cell fusion with polyethylene glycol revealed that the patient belonged to group F. He died of bile duct cancer at the age of 50. This is the first report of an XP-F patient with neurological abnormalities.
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PMID:A case of xeroderma pigmentosum complementation group F with neurological abnormalities. 842 28

The present paper describes the radiobiological effects induced by an exposure to ionizing radiation and their pathogenesis. The different skin reactions are described in detail because of their importance and frequency. Thus the acute skin lesions after high doses and the late effects resulting, either from high doses, or from accumulation of chronic irradiation, are studied. The main early syndromes are then characterized: neurological, gastro-intestinal, bone-marrow and prodromic. As far as the complex problem of radiocarcinogenesis is concerned, the main results derived from studies by international organizations such as the ICRP and the UNSCEAR are reported: risk coefficient of 5% per gray, for lethal radioinduced cancer, after total body irradiation, at low dose of low-LET radiation. The effects of irradiation in utero are then considered: risk of malformation after irradiation during the two first months of pregnancy and risk of mental retardation after irradiation during the third and the fourth months. Finally, the genetic risk is presented as being equal to one fourth of the risk of carcinogenesis at low doses. The effects of irradiation on the gonads are also described.
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PMID:[Exposure to ionizing radiation: radiobiological and pathogenic effects (2)]. 868 52

After an introduction, three selected contributions to the 10th Course on Radiation Protection held at the University Hospital of Basel are presented. The principles of radiation protection and new Swiss legislation are discussed as the basis for radiological protection. Ways are proposed of reducing radiation exposure while optimizing the X-ray picture with a minimum dose to patient and personnel. Radiation effects from low doses. From the beginning, life on this planet has been exposed to ionizing radiation from natural sources. For about one century additional irradiation has reached us from man-made sources as well. In Switzerland the overall annual radiation exposure from ambient and man-made sources amounts to about 4 mSv. The terrestrial and cosmic radiation and natural radionuclids in the body cause about 1.17 mSv (29%). As much as 1.6 mSv (40%) results from exposure to radon and its progenies, primarily inside homes. Medical applications contribute approximately 1 mSv (26%) to the annual radiation exposure and releases from atomic weapons, nuclear facilities and miscellaneous industrial operations yield less than 0.12 mSv (< 5%) to the annual dose. Observations of detrimental radiation effects from intermediate to high doses are challenged by observations of biopositive adaptive responses and hormesis following low dose exposure. The important question, whether cellular adaptive response or hormesis could cause beneficial effects to the human organism that would outweigh the detrimental effects attributed to low radiation doses, remains to be resolved. Whether radiation exerts a detrimental, inhibitory, modifying or even beneficial effect is likely to result from identical molecular lesions but to depend upon their quantity, localization and time scale of initiation, as well as the specific responsiveness of the cellular systems involved. For matters of radiation protection the bionegative radiation effects are classified as deterministic effects or stochastic effects respectively. The various histopathological reactions of tissues and organs following localized tissue irradiation, and the radiation syndromes following total body irradiation, constitute the deterministic effects. There will be a threshold below which deterministic effects do not appear and spontaneous incidences are not known. For low dose risk considerations deterministic effects are of no significance. Genetic effects and carcinogenesis are said to be stochastic effects. Characteristically the probability of stochastic effects increases with dose but the severity of the effects is independent of the dose. The shape of the dose-response relationship at intermediate to high dose levels is linear-quadratic. For exposure to low doses the response becomes linear, as is to be expected for a linear-quadratic function at low dose. No threshold is assumed for stochastic effects. The estimate of probability of fatal cancer by the ICRP is 4 x 10(-2) per Sv for the working population and 5 x 10(-2) per Sv for the total population. Their estimate of probability of serious hereditary disorders within the first two generations is 1 x 10(-2) per Sv. The highest probability coefficient is attributed to mental retardation following exposure in utero. Within the sensitive period at 8-15 weeks of gestation, a risk probability of 40 x 10(-2) per Sv is assumed but a threshold at 0.1 Sv is not excluded. Conclusions drawn from experiments, clinical observations and epidemiological studies following intermediate to high radiation exposures attribute a mutagenic and carcinogenic competence to all radiation doses. Microdosimetric considerations support this assumption. This conclusion cannot be confirmed experimentally nor by epidemiological studies of populations living under different conditions from natural sources of radiation. Nevertheless, a change in the present restrictive radiation protection policy does not yet appear appropriate.
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PMID:[Basis of radiation protection]. 871 64


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