Person: García Pérez, Miguel Ángel
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First Name
Miguel Ángel
Last Name
García Pérez
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Psicología
Department
Psicobiología y Metodología en Ciencias del Comportamiento
Area
Metodología de las Ciencias del Comportamiento
Identifiers
4 results
Search Results
Now showing 1 - 4 of 4
Item Cathepsin C gene: First compound heterozygous patient with Papillon-Lefèvre syndrome and a novel symptomless mutation(Human Mutation: Variation, Informatics and Disease, 2001) Allende Martínez, Luis Miguel; García Pérez, Miguel Ángel; Moreno, Ángel; Corell, Alfredo; Carasol, Miguel; Martínez Canut, Pedro; Arnaiz Villena, AntonioPapillon-Lefèvre syndrome (PLS) has recently been shown to be caused by mutations in the cathepsin C gene resulting in periodontal disease and palmoplantar keratosis. Thirteen different homozygous mutations have been characterised in PLS patients of different ethnic origin. In the present paper, a PLS patient is described who carries two novel mutations (706G>T and 872G>A) in the paternal and maternal chromosomes, respectively. This is the first compound patient described so far. In addition, a novel symptomless mutation (458C>T) in the cathepsin C gene is described in three homozygous individuals. Thus, not all mutations should be considered as a cause of disease, whether case studies or general population screening is performed. Another already described mutation that provoked the Haim-Munk syndrome (HMS) in Indian Jews has also been found to give rise to PLS in a Spanish family from Madrid. On the other hand, PLS patients are ameliorated by retinoids, which indicates that retinoids may be used as therapeutic agents in this immune system deficiency.Item Novel mutations and defective protein kinase C activation of T-lymphocytes in ataxia telangiectasia(Clinical and Experimental Immunology, 2001) García Pérez, Miguel Ángel; Allende Martínez, Luis Miguel; Corell, A.; Varela, P.; Moreno, A. A.; Sotoca, A.; Moreno, Ángel; Paz Artal, Estela Natividad; Barreiro, E.; Arnaiz Villena, AntonioSummary: 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.Item A novel CD18 genomic deletion in a patient with severe leucocyte adhesion deficiency: a possible CD2/lymphocyte function‐associated antigen‐1 functional association in humans(2000) Allende Martínez, Luis Miguel; Hernández, Manuel; Corell, A.; García Pérez, Miguel Ángel; Varela, P.; Moreno, Ángel; Guillén Perales, J.; Arnaiz Villena, AntonioLeucocyte adhesion deficiency (LAD) is an autosomal‐recessive genetic disease that is characterized clinically by severe bacterial infections and caused by mutations in the CD18 gene that codes for the β2 integrin subunit. A patient with a severe LAD phenotype was studied and the molecular basis of the disease was identified as a single homozygous defect in a Herpes virus saimiri (HVS)‐transformed T‐cell line. The defect identified involves a deletion of 171 bp in the cDNA that encodes part of the proteic extracellular domain. This genetic abnormality was further studied at the genomic DNA level and found to consist of a deletion of 169 bp (from − 37 of intron 4 to + 132 of exon 5), which abolishes the normal splicing and results in the total skipping of exon 5. The 171‐bp shortened ‘in‐frame’ mRNA not only resulted in the absence of CD18 expression on the cell surface but also in its absence in the cytoplasm of HVS T‐cell lines. Functionally, the LAD‐derived HVS T‐cell lines showed a severe, selective T‐cell activation impairment in the CD2 (but not in the CD3) pathway. This defect was not reversible when exogenous interleukin‐2 (IL‐2) was added, suggesting that there is also a functional interaction of the lymphocyte function‐associated antigen‐1 (LFA‐1) protein in the CD2 signal transduction pathway in human T cells, as has been previously reported in mice and in the human Papillon–Lefèvre syndrome. Thus, HVS transformation is not only a suitable model for T‐cell immunodeficiency studies and characterization, but is also a good system for investigating the immune system in pathological conditions. It may also be used in the future in cellular models for in vitro gene‐therapy trials.Item A Point Mutation in a Domain of Gamma Interferon Receptor 1 Provokes Severe Immunodeficiency(Clinical and Diagnostic Laboratory Immunology, 2001) Allende Martínez, Luis Miguel; López Goyanes, Alberto; Paz Artal, Estela Natividad; Corell, Alfredo; García Pérez, Miguel Ángel; Varela Peña, Pilar; Scarpellini, Atilio; Negreira, Sagrario; Palenque Mataix, Elia; Arnaiz Villena, AntonioGamma interferon (IFN-γ) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN-γ receptor ligand-binding chain (IFN-γR1) deficiency present gross mutations that truncate the protein and prevent its expression, giving rise to severe mycobacterial infections and, frequently, a fatal outcome. In this report a new mutation that affects the IFN-γR1 ligand-binding domain in a Spanish patient with mycobacterial disseminated infection and multifocal osteomyelitis is characterized. The mutation generates an amino acid change that does not abrogate protein expression on the cellular surface but that severely impairs responses after the binding of IFN-γ (CD64 and HLA class II induction and tumor necrosis factor alpha and interleukin-12 production). A patient's younger brother, who was also probably homozygous for the mutation, died from meningitis due to Mycobacterium bovis. These findings suggest that a point mutation may be fatal when it affects functionally important domains of the receptor and that the severity is not directly related to a lack of IFN-γ receptor expression. Future research on these nontruncating mutations will make it possible to develop new therapeutical alternatives in this group of patients.