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

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

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 radio-induced 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 effects and pathogenesis. 1]. 872 Sep 71

Gorlin syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinomas, medulloblastomas, ovarian fibromas, and a variety of developmental defects. All affected individuals share certain key features, but there is significant phenotypic variability within and among kindreds with respect to malformations. The gene (NBCCS) maps to chromosome 9q22, and allelic loss at this location is common in tumors from Gorlin syndrome patients. Two recessive cancer-predisposition syndromes, xeroderma pigmentosum group A (XPAC) and Fanconi anemia group C (FACC), map to the NBCCS region; and unusual, dominant mutations in these genes have been proposed as the cause of Gorlin syndrome. This study presents cytogenetic and molecular characterization of germ-line deletions in one patient with a chromosome 9q22 deletion and in a second patient with a deletion of 9q22-q3l. Both have typical features of Gorlin syndrome plus additional findings, including mental retardation, conductive hearing loss, and failure to thrive. That Gorlin syndrome can be caused by null mutations (deletions) rather than by activating mutations has several implications. First, in conjunction with previous analyses of allelic loss in tumors, this study provides evidence that associated neoplasms arise with homozygous inactivation of the gene. In addition, dominant mutations of the XPAC and FACC1 genes can be ruled out as the cause of Gorlin syndrome, since the two patients described have null mutations. Finally, phenotypic features that show variable expression must be influenced by genetic background, epigenetic effects, somatic mutations, or environmental factors, since these two patients with identical alterations (deletions) of the Gorlin syndrome gene have somewhat different manifestations of Gorlin syndrome.
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PMID:Molecular analysis of chromosome 9q deletions in two Gorlin syndrome patients. 875 29

The Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, which belongs to the family of genetically determined instability syndromes and to the growing category of ataxia telangiectasia (AT)--related disorders. The main manifestations include pronounced microcephaly with mental retardation in most patients, "bird-like" facies, growth retardation, immunodeficiency, chromosome instability with multiple chromosome 7 and 14 rearrangements, hypersensitivity to ionizing radiation and normal AFP level. In light of high predisposition to malignancy, an accurate diagnosis is very important for the patient.
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PMID:[Microcephaly with chromosomal instability and immunodeficiency--Nijmegen syndrome]. 896 94

Trichothiodystrophy (TTD) is a rare, autosomal recessive disorder characterized by sulfur-deficient brittle hair and nails, mental retardation, impaired sexual development, and ichthyosis. Photosensitivity has been reported in approximately 50% of the cases, but no skin cancer is associated with TTD. Virtually all photosensitive TTD patients have a deficiency in the nucleotide excision repair (NER) of UV-induced DNA damage that is indistinguishable from that of xeroderma pigmentosum (XP) complementation group D (XP-D) patients. DNA repair defects in XP-D are associated with two additional, quite different diseases; XP, a sun-sensitive and cancer-prone repair disorder, and Cockayne syndrome (CS), a photosensitive condition characterized by physical and mental retardation and wizened facial appearance. One photosensitive TTD case constitutes a new repair-deficient complementation group, TTD-A. Remarkably, both TTD-A and XP-D defects are associated with subunits of TFIIH, a basal transcription factor with a second function in DNA repair. Thus, mutations in TFIIH components may, on top of a repair defect, also cause transcriptional insufficiency, which may explain part of the non-XP clinical features of TTD. Besides XPD and TTDA, the XPB gene product is also part of TFIIH. To date, three patients with the remarkable conjunction of XP and CS but not TTD have been assigned to XP complementation group B (XP-B). Here we present the characterization of the NER defect in two mild TTD patients (TTD6VI and TTD4VI) and confirm the assignment to X-PB. The causative mutation was found to be a single base substitution resulting in a missense mutation (T119P) in a region of the XPB protein completely conserved in yeast, Drosophila, mouse, and man. These findings define a third TTD complementation group, extend the clinical heterogeneity associated with XP-B, stress the exclusive relationship between TTD and mutations in subunits of repair/transcription factor TFIIH, and strongly support the concept of "transcription syndromes."
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PMID:A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy. 901 5

The aim of the study was to determine whether consanguineous marriages result in reproductive wastage and an increased incidence of illness in the offspring in a community with a long history of inbreeding and an expected high rate of consanguineous marriage. A representative sample of 2200 women aged > or = 15 years from Dubai and Al Ain, two cities in the United Arab Emirates, representing on the one hand a modern metropolis and on the other a traditional society, were studied. A questionnaire, which included questions on age, parity, gravidity, number of stillbirths, number of abortions, number of children alive, neonatal deaths and specific illnesses in children, was administered by nurses in antenatal and gynaecological clinics in the two cities. The rate of consanguineous marriage was 50.5% and parity, gravidity, ages and number of children were similar in consanguineous and non-consanguineous groups. There was no significant difference in rates of abortion, stillbirth and neonatal death between the two groups. Overall, there was statistically significant higher reproductive wastage in consanguineous couples, but when the category of less than second cousins was excluded from the consanguineous group no difference was found in reproductive wastage between consanguineous and non-consanguineous marriages. Children born to consanguineous unions also had significantly higher incidences of illnesses (37.1%) than those of non-consanguineous unions (29%). The occurrence of malignancies, congenital abnormalities, mental retardation and physical handicap was significantly higher in offspring of consanguineous than non-consanguineous marriages. In conclusion, consanguinity did not result in reproductive wastage, but was found to be an important factor in the causation of specific illnesses in offspring.
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PMID:A study of possible deleterious effects of consanguinity. 913 81

We report an innovative fluorescence in situ hybridization technique which exploits a unique resource of 41 telomere-specific probes and allows the simultaneous analysis of the subtelomeric region of every chromosome for deletion, triplication and balanced translocation events. This technique requires only a single microscope slide per patient and is expected to be a useful diagnostic tool with applications in the fields of idiopathic mental retardation, the detection of congenital abnormalities and in some forms of cancer. This will lead to more accurate genetic counselling of patients and their families and will provide the basis for future diagnostic, therapeutic and preventative measures.
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PMID:Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres. 915 14

In a previous large scale screen for differentially expressed genes in pancreatic cancer, we identified a gene highly overexpressed in cancer encoding a novel protein with four K-homologous (KH) domains. KH-domains are found in a subset of RNA-binding proteins, including pre-mRNA-binding (hnRNP) K protein and the fragile X mental retardation gene product (FMR1). By fluorescence in situ hybridization (FISH) the identified gene named koc (KH domain containing protein overexpressed in cancer) was assigned to chromosome 7p11.5. Two pseudogenes were localised on chromosome 6 and 11. The cloned koc cDNA has a 250 bp 5'-UTR, a 1740 bp ORF and a 2168 bp 3'-UTR. The AU-rich 3'-untranslated region of koc contains eight AUUUA and four AUUUUUA reiterated motifs. The deduced koc protein with 580 amino-acids has a relative molecular mass (Mr) of approximately 65,000 (65 K). The koc transcript is highly overexpressed in pancreatic cancer cell lines and in pancreatic cancer tissue as compared to both, normal pancreas and chronic pancreatitis tissue. High levels of expression were as well found in tissue samples of other human tumours. As the KH domain has been shown to be involved in the regulation of RNA synthesis and metabolism, we speculate that koc may assume a role in the regulation of tumour cell proliferation by interfering with transcriptional and or posttranscriptional processes. However, the precise role of koc in human tumour cells is unknown and remains to be elucidated.
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PMID:Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein. 917 71


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