FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2079052854> ?p ?o ?g. }

• W2079052854 endingPage "561" @default.
• W2079052854 startingPage "551" @default.
• W2079052854 abstract "SummaryAtaxia-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. 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." @default.
• W2079052854 created "2016-06-24" @default.
• W2079052854 creator A5004896170 @default.
• W2079052854 creator A5058528594 @default.
• W2079052854 creator A5060390908 @default.
• W2079052854 creator A5060594068 @default.
• W2079052854 creator A5063387040 @default.
• W2079052854 creator A5067359802 @default.
• W2079052854 creator A5079978565 @default.
• W2079052854 creator A5080088757 @default.
• W2079052854 creator A5082694913 @default.
• W2079052854 creator A5086398854 @default.
• W2079052854 date "1998-03-01" @default.
• W2079052854 modified "2023-10-17" @default.
• W2079052854 title "Genotype-Phenotype Relationships in Ataxia-Telangiectasia and Variants" @default.
• W2079052854 cites W11549471 @default.
• W2079052854 cites W132489834 @default.
• W2079052854 cites W1485934389 @default.
• W2079052854 cites W1487477578 @default.
• W2079052854 cites W1492529596 @default.
• W2079052854 cites W1493323052 @default.
• W2079052854 cites W1507800813 @default.
• W2079052854 cites W1507919027 @default.
• W2079052854 cites W1588888865 @default.
• W2079052854 cites W1964968464 @default.
• W2079052854 cites W1965051773 @default.
• W2079052854 cites W1965161960 @default.
• W2079052854 cites W1967264277 @default.
• W2079052854 cites W1969424937 @default.
• W2079052854 cites W1971728749 @default.
• W2079052854 cites W1972440247 @default.
• W2079052854 cites W1973969831 @default.
• W2079052854 cites W1982917678 @default.
• W2079052854 cites W1988498014 @default.
• W2079052854 cites W1989527307 @default.
• W2079052854 cites W1998762942 @default.
• W2079052854 cites W2003832230 @default.
• W2079052854 cites W2004486431 @default.
• W2079052854 cites W2007572106 @default.
• W2079052854 cites W2008684482 @default.
• W2079052854 cites W2011788692 @default.
• W2079052854 cites W2030720512 @default.
• W2079052854 cites W2034436703 @default.
• W2079052854 cites W2044923350 @default.
• W2079052854 cites W2046556531 @default.
• W2079052854 cites W2046994769 @default.
• W2079052854 cites W2049457436 @default.
• W2079052854 cites W2052121157 @default.
• W2079052854 cites W2052598236 @default.
• W2079052854 cites W2055499468 @default.
• W2079052854 cites W2062232773 @default.
• W2079052854 cites W2067191626 @default.
• W2079052854 cites W2074031999 @default.
• W2079052854 cites W2075906592 @default.
• W2079052854 cites W2078242581 @default.
• W2079052854 cites W2078378661 @default.
• W2079052854 cites W2085252163 @default.
• W2079052854 cites W2094497313 @default.
• W2079052854 cites W2097316296 @default.
• W2079052854 cites W2107565104 @default.
• W2079052854 cites W2122869827 @default.
• W2079052854 cites W2123304039 @default.
• W2079052854 cites W2130326940 @default.
• W2079052854 cites W2139612403 @default.
• W2079052854 cites W2140107851 @default.
• W2079052854 cites W2149386502 @default.
• W2079052854 cites W2151968619 @default.
• W2079052854 cites W2153923420 @default.
• W2079052854 cites W2158728679 @default.
• W2079052854 cites W2159168998 @default.
• W2079052854 cites W2168347953 @default.
• W2079052854 cites W2169830490 @default.
• W2079052854 cites W2170085947 @default.
• W2079052854 cites W2172192445 @default.
• W2079052854 cites W2398064360 @default.
• W2079052854 cites W2416722388 @default.
• W2079052854 cites W50377807 @default.
• W2079052854 doi "https://doi.org/10.1086/301755" @default.
• W2079052854 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1376949" @default.
• W2079052854 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9497252" @default.
• W2079052854 hasPublicationYear "1998" @default.
• W2079052854 type Work @default.
• W2079052854 sameAs 2079052854 @default.
• W2079052854 citedByCount "231" @default.
• W2079052854 countsByYear W20790528542012 @default.
• W2079052854 countsByYear W20790528542013 @default.
• W2079052854 countsByYear W20790528542014 @default.
• W2079052854 countsByYear W20790528542015 @default.
• W2079052854 countsByYear W20790528542016 @default.
• W2079052854 countsByYear W20790528542017 @default.
• W2079052854 countsByYear W20790528542018 @default.
• W2079052854 countsByYear W20790528542019 @default.
• W2079052854 countsByYear W20790528542020 @default.
• W2079052854 countsByYear W20790528542021 @default.
• W2079052854 countsByYear W20790528542022 @default.
• W2079052854 countsByYear W20790528542023 @default.
• W2079052854 crossrefType "journal-article" @default.
• W2079052854 hasAuthorship W2079052854A5004896170 @default.

• next