title: Adult-onset ataxia telangiectasia due to ATM 5762ins137 mutation homozygosity.
abstract: Ataxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder that arises because of mutations in the ATM gene. The 5762ins137 A-->G point mutation activates a cryptic splice donor site resulting in a 137 bp intronic insert being aberrantly spliced into the ATM transcript. However, normal ATM transcript also is produced from this affected allele, albeit at significantly reduced levels. An exceptionally mild A-T phenotype occurs as a result of homozygosity for the 5762ins137 mutation because of relative preservation of ATM protein expression/kinase activity.
authors.affiliation: Queen Elizabeth Neuroscience Centre, Queen Elizabeth Hospital, Edgbaston, Birmingham. iansutton@email.com
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Sutton
authors.forename: James I K
authors.initials: JI
authors.lastname: Last
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ritchie
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Harrington
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Byrd
authors.forename: A Malcolm R
authors.initials: AM
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000409:Alanine / Q000235:genetics; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins; D001773:Blood Cells / Q000378:metabolism / Q000528:radiation effects; D015153:Blotting, Western / Q000379:methods; D018797:Cell Cycle Proteins; D002460:Cell Line; D002531:Cerebellum / Q000473:pathology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005998:Glycine / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010766:Phosphorylation; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D022821:RNA Splice Sites; D011836:Radiation Tolerance / Q000235:genetics; D012694:Serine; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D022821:RNA Splice Sites; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D012694:Serine; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000409:Alanine; D005998:Glycine