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)

A case report of an apparently unique progeroid syndrome is reported here. Major clinical characteristics included growth failure with onset of senility in the early teens, atrophic skin, hypogonadism, and retinal and vascular sclerosis. Mental retardation was present, but could have been attributable to trauma. The replicative life spans of several lines of cultured skin fibroblasts were within the normal range, in contrast to the limited life-spans of such cultures from patients with Werner's syndrome, whom our patient most closely resembles. Also, in contrast to Werner's syndrome, our patient did not have white or gray hair or cataracts.
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PMID:Children who age rapidly--progeroid syndromes: case report of a new variant. 83 28

The case of a 40-year-old woman with Werner's syndrome associated with systemic lupus erythematosus (SLE) is reported. The patient exhibited short stature, slender extremities, thinned hair, high-pitched voice, cataracts, ulceration of the fingers, and mental retardation. Malar erythema, photosensitivity, and proteinuria had been noted since age 34. The serum contained high titers of antibodies to dsDNA, Sm, nRNP, and SS-A/Ro. The simultaneous presence of Werner's syndrome and SLE could be a coincidental occurrence of the two diseases, although it might be due to an abnormality in replication or degeneration of DNA leading to the development of both diseases.
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PMID:A case of Werner's syndrome associated with systemic lupus erythematosus. 778 63

A 33-year-old woman, whose parents were consanguineously married, was admitted to our hospital because of progressive difficulty in walking and hoarseness in speech. She had been in good health as a child, at age 16 ulcerations appeared on the skin of feet, and have been recurrent. AT age 22, bilateral cataracts were removed. From the age of 26 years, the deformities in the toes and fingers worsened and she had difficulty in walking. At age 32, hoarseness was noticed. The patient was a diminutive woman and the skin was dry, thin and hyperpigmented. The neurological examination revealed mental retardation, spastic paraparesis and polyneuropathy. Electrophysiological studies revealed a slowing of central and peripheral nerve conduction. Sural nerve biopsy revealed a significantly higher incidence of de- and remyelination and a loss of myelinated fibers. These data suggest that the central and peripheral nervous systems are affected in Werner syndrome.
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PMID:[A case of Werner syndrome associated with spastic paraparesis and peripheral neuropathy]. 839 17

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.
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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

Six known or predicted helicases that are mutated in human syndromes are now recognized. These syndromes include xeroderma pigmentosum, Cockayne's syndrome, trichothiodystrophy, Bloom's syndrome, Werner's syndrome, and alpha-thalassemia mental retardation on the X chromosome. The clinical abnormalities in these syndromes cover a broad spectrum, pointing to different cellular processes of DNA manipulation that are defective in these syndromes.
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PMID:DNA helicases in inherited human disorders. 922 11

A 28-year old woman developed juvenile lung cancer. Cockayne syndrome, one of the progeroid syndromes, was suspected because of mental retardation, renal disfunction, photosensitivity, and the characteristic physical appearance such as low set ears, microcephaly, senile face, short stature, and cachectic habitus. We tried chemotherapy with gefitinib and docetaxel, but they were ineffective and she was found to have multiple extraocular muscle metastasis. CT scan showed carcinomatous lymphangiosis findings, her respiratory condition worsened gradually and she died about 7 months after the diagnosis of lung cancer. Some progeroid syndromes are known for their high incidence of juvenile cancres, and the responsible genes are gradually coming to light. However, concerning the relationship between lung cancer and progeroid syndromes, our investigations revealed only one case report of Werner syndrome, one of the progeroid syndromes, accompanied by lung cancer. Progeroid syndromes with lung cancer are thought to be very rare. We expect collection of data on cases like the present case will help to clarify the mechanism of aging and carcinogenesis.
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PMID:[A case of juvenile lung cancer with suspected progeroid syndrome and mental retardation]. 1741 42

Complex chromosome rearrangements (CCRs) are currently defined as structural genome variations that involve more than 2 chromosome breaks and result in exchanges of chromosomal segments. They are thought to be extremely rare, but their detection rate is rising because of improvements in molecular cytogenetic technology. Their population frequency is also underestimated, since many CCRs may not elicit a phenotypic effect. CCRs may be the result of fork stalling and template switching, microhomology-mediated break-induced repair, breakage-fusion-bridge cycles, or chromothripsis. Patients with chromosomal instability syndromes show elevated rates of CCRs due to impaired DNA double-strand break responses during meiosis. Therefore, the putative functions of the proteins encoded by ATM, BLM, WRN, ATR, MRE11, NBS1, and RAD51 in preventing CCRs are discussed. CCRs may exert a pathogenic effect by either (1) gene dosage-dependent mechanisms, e.g. haploinsufficiency, (2) mechanisms based on disruption of the genomic architecture, such that genes, parts of genes or regulatory elements are truncated, fused or relocated and thus their interactions disturbed - these mechanisms will predominantly affect gene expression - or (3) mixed mutation mechanisms in which a CCR on one chromosome is combined with a different type of mutation on the other chromosome. Such inferred mechanisms of pathogenicity need corroboration by mRNA sequencing. Also, future studies with in vitro models, such as inducible pluripotent stem cells from patients with CCRs, and transgenic model organisms should substantiate current inferences regarding putative pathogenic effects of CCRs. The ramifications of the growing body of information on CCRs for clinical and experimental genetics and future treatment modalities are briefly illustrated with 2 cases, one of which suggests KDM4C (JMJD2C) as a novel candidate gene for mental retardation.
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PMID:Mechanisms of Origin, Phenotypic Effects and Diagnostic Implications of Complex Chromosome Rearrangements. 2673 13