Novel mutations and defective protein kinase C activation of T-lymphocytes in ataxia telangiectasia

García Pérez, Miguel ÁngelAllende Martínez, Luis MiguelCorell, A.Varela, P.Moreno, A. A.Sotoca, AndrésMoreno, ÁngelPaz Artal, Estela NatividadBarreiro, E.Arnaiz Villena, Antonio2024-02-022024-02-022001-03-01García-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: PMC1906002.1365-22490009-910410.1046/j.1365-2249.2001.01452.xhttps://hdl.handle.net/20.500.14352/98064Summary: 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 &gt; 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 &gt; 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.engNovel mutations and defective protein kinase C activation of T-lymphocytes in ataxia telangiectasiajournal articlehttps://academic.oup.com/cei/article/123/3/472/6461505?login=truehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906002/open access616-009.26612.017ataxia-telangiectasiaPKCPMAimmunodeficienciesCiencias Biomédicas32 Ciencias Médicas