RT Journal Article
T1 Novel mutations and defective protein kinase C activation of T-lymphocytes in ataxia telangiectasia
A1 García Pérez, Miguel Ángel
A1 Allende Martínez, Luis Miguel
A1 Corell, A.
A1 Varela, P.
A1 Moreno, A. A.
A1 Sotoca, Andrés
A1 Moreno, Ángel
A1 Paz Artal, Estela Natividad
A1 Barreiro, E.
A1 Arnaiz Villena, Antonio
AB Summary: 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.
PB Oxford University Press
SN 1365-2249
SN 0009-9104
YR 2001
FD 2001-03-01
LK https://hdl.handle.net/20.500.14352/98064
UL https://hdl.handle.net/20.500.14352/98064
LA eng
NO García-Pérez MA, Allende LM, Corell A, Varela P, Moreno AA, Sotoca A, Moreno A, Paz-Artal E, Barreiro E, Arnaiz-Villena A. Novel mutations and defective protein kinase C activation of T-lymphocytes in ataxia telangiectasia. Clin Exp Immunol. 2001 Mar;123(3):472-80. doi: 10.1046/j.1365-2249.2001.01452.x. PMID: 11298136; PMCID: PMC1906002.
NO Ministerio de Educación y Ciencia
NO Comunidad Autónoma de Madrid
DS Docta Complutense
RD 6 abr 2025