title: Novel mutations and defective protein kinase C activation of T-lymphocytes in ataxia telangiectasia.
abstract: Three ataxia telangiectasia (AT) patients have been characterized immunologically and molecularly. Patient 1 presents two nondescribed splicing mutations which affect exons 15 and 21 of the ATM gene. The maternal defect consists of a G > A transition in the first nucleotide of the intron 21 donor splicing site which results in a complete deletion of exon 21. The paternal mutation consists of an A > C transversion in the intron 14 acceptor splicing site which produces a partial skipping of exon 15. Two abnormal alternative transcripts were found, respectively, 17 and 41 nucleotides shorter. Patient 2 presents a homozygous genomic deletion of 28 nucleotides in the last exon of the gene. This deletion changes the normal reading frame after residue 3003 of the protein and introduces a premature stop codon at residue 3008 that could originate a truncated ATM protein. Patient 3, a compound heterozygote, presents a defect which consists of a G > A transition in the first nucleotide of intron 62 donor splicing site which results in a complete deletion of exon 62. The results obtained during a three year period in the proliferation assays show an impaired PMA (phorbol myristate acetate) activation in specific T lymphocyte activation pathways (CD69, CD26, CD28, CD3, PHA, PWM and Con A mediated) but not in others (CD2, ionomycin, and Ig surface receptor). The possible link among specific ATM mutations and abnormal immune responses is unknown.
authors: Department of Immunology, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors: M A
authors: MA
authors: García-Pérez
authors: L M
authors: LM
authors: Allende
authors: A
authors: A
authors: Corell
authors: P
authors: P
authors: Varela
authors: A A
authors: AA
authors: Moreno
authors: A
authors: A
authors: Sotoca
authors: A
authors: A
authors: Moreno
authors: E
authors: E
authors: Paz-Artal
authors: E
authors: E
authors: Barreiro
authors: A
authors: A
authors: Arnaiz-Villena
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D002648:Child; D002871:Chromosome Banding; D019457:Chromosome Breakage; D005260:Female; D006579:Heterozygote; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D009154:Mutation; D010290:Parents; D011493:Protein Kinase C / Q000378:metabolism*; D012326:RNA Splicing; D015398:Signal Transduction / Q000235:genetics; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011493:Protein Kinase C