Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten of 18 children in a highly inbred Arab kindred suffered from either ataxia telangiectasia (AT) or a variant syndrome consisting of ataxia, microcephaly, and congenital cataract (AMC). Four of the nine afflicted children were treated in our unit when they developed lymphomas (both Hodgkin's and non-Hodgkin's including Burkitt's). They were given chemotherapy (either standard COMP or low-dose ABV/CVPP). The children with non-Hodgkin's lymphomas died of sepsis after receiving full-dose COMP. Low-dose ABV/CVPP brought about a 20-month remission in one child with nodular sclerosing Hodgkin's lymphoma and both AT and AMC, but she developed a preleukemic syndrome and her parents refused further treatment; she too died. A fourth child, also with nodular sclerosing Hodgkin's lymphoma, is currently in complete remission after ABV/CVPP. Treatment of lymphomas in patients with AT is extraordinarily difficult and has potential side effects so grave as to necessitate careful monitoring and individualized protocols.
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PMID:Ataxia telangiectasia and lymphoma: an indication for individualized chemotherapy dosing--report of treatment in a highly inbred Arab family. 762 85

The report describes two unrelated male children, aged 6 and 8 years, respectively, with congenital periodic alternating nystagmus, congenital strabismus, microcephaly with cortical and cerebellar hypoplasia, mental retardation, low stature, and bat ears. Karyotypes were normal. Neuropediatric and ophthalmologic examinations, radiologic imaging of the brain, and laboratory analyses were performed to exclude other causes of periodic alternating nystagmus, such as ataxia-telangiectasia, acquired disease of the caudal brainstem or the cerebellum, albinism, or loss of vision resulting from cataract or vitreous hemorrhage. The similar morphologic and clinical features of both patients raise the possibility that they have an identical syndrome.
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PMID:Periodic alternating nystagmus in two children with a similar, unusual phenotype. 1111 1

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.
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PMID:Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts. 1211 22

Previous studies have shown that the eyes of ATM heterozygous mice exposed to low-LET radiation (X-rays) are significantly more susceptible to the development of cataracts than are those of wildtype mice. The findings, as well as others, run counter to the assumption underpinning current radiation safety guidelines, that individuals are all equally sensitive to the biological effects of radiation. A question, highly relevant to human space activities is whether or not, in similar fashion there may exist a genetic predisposition to high-LET radiation damage. Mice haplodeficient for the ATM gene and wildtypes were exposed to 325 mGy of 1 GeV/amu 56Fe ions at the AGS facility of Brookhaven National Laboratory. The fluence was equivalent to 1 ion per lens epithelial cell nuclear area. Controls consisted of irradiated wildtype as well as unirradiated wildtype and heterozygous mice. Prevalence analyses for stage 0.5-3.0 cataracts indicated that not only cataract onset but also progression were accelerated in the mice haplo-deficient for the ATM gene. The data show that heterozygosity for the ATM gene predisposes the eye to the cataractogenic influence of heavy ions and suggest that ATM heterozygotes in the human population may also be radiosensitive. This may have to be considered in the selection of individuals who will be exposed to both HZE particles and low-LET radiation as they may be predisposed to increased late normal tissue damage.
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PMID:Mice heterozygous for the ATM gene are more sensitive to both X-ray and heavy ion exposure than are wildtypes. 1593 3

This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated (ATM) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele. The molecular assay on human tissue samples discovered that ATM expression was down-regulated in majority of ARC tissues and correlated with ATM genotypes. In addition, the Comet assay of cellular DNA damage of peripheral lymphocytes indicated that individuals carrying the G allele (GG/GT) of ATM-rs4585 had lower DNA breaks compared to individuals with TT genotype. These findings suggested that the SNP rs4585 in ATM might affect ARC risk through modulating the regulatory affinity of miR-2964a-5p. The reduced DSBs repair might be involved in ARC pathogenesis.
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PMID:MiR-2964a-5p binding site SNP regulates ATM expression contributing to age-related cataract risk. 2915 95