Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome
| Autor: | Najla Mekki, S. Ben Becher, N. Matoussi, Mohamed-Ridha Barbouche, Meriem Ben-Ali, Nourhen Agrebi, Beya Larguèche, Imen Ben-Mustapha, M. Ben-Ahmed, N Dhouib, Mohamed Bejaoui |
|---|---|
| Přispěvatelé: | Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage, Université de Tunis El Manar (UTM), Faculté de Médecine de Tunis, Béchir Hamza Children's Hospital, Centre National de Greffe de la Moëlle osseuse Tunis (CNGMO), This work was supported by the Tunisian ministry of higher education and research. |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine [SDV]Life Sciences [q-bio] Autosomal recessive medicine.disease_cause Splicing Severity of Illness Index Germline MESH: fas Receptor/blood MESH: fas Receptor/genetics Exon Consanguinity 0302 clinical medicine MESH: Reverse Transcriptase Polymerase Chain Reaction MESH: Germ-Line Mutation MESH: Fas Ligand Protein/blood Immunology and Allergy Genetics Mutation education.field_of_study Reverse Transcriptase Polymerase Chain Reaction MESH: Real-Time Polymerase Chain Reaction MESH: Libya Fas receptor MESH: Infant Interleukin-10 RNA splicing [SDV.IMM]Life Sciences [q-bio]/Immunology MESH: Autoimmune Lymphoproliferative Syndrome/genetics MESH: Tunisia Fas Ligand Protein Tunisia MESH: Alternative Splicing/genetics Blotting Western Immunology Population Libya Biology Real-Time Polymerase Chain Reaction MESH: Autoimmune Lymphoproliferative Syndrome/blood 03 medical and health sciences MESH: Severity of Illness Index medicine Humans MESH: Blotting Western fas Receptor education Germ-Line Mutation MESH: Consanguinity MESH: Humans Autoimmune Lymphoproliferative Syndrome Alternative splicing Alps Infant FAS medicine.disease MESH: Male Alternative Splicing 030104 developmental biology Autoimmune lymphoproliferative syndrome 030215 immunology MESH: Interleukin-10/blood |
| Zdroj: | Clinical Immunology Clinical Immunology, Elsevier, 2017, 183, pp.17-23. ⟨10.1016/j.clim.2017.06.009⟩ |
| ISSN: | 1521-6616 1521-7035 |
| DOI: | 10.1016/j.clim.2017.06.009⟩ |
| Popis: | International audience; Autoimmune lymphoproliferative syndrome (ALPS) is a prototypic disorder of impaired apoptosis characterized by autoimmune features and lymphoproliferation. Heterozygous germline or somatic FAS mutations associated with preserved protein expression have been described. Very rare cases of homozygous germline FAS mutations causing severe autosomal recessive form of ALPS with a complete defect of Fas expression have been reported. We report two unrelated patients from highly inbred North African population showing a severe ALPS phenotype and an undetectable Fas surface expression. Two novel homozygous mutations have been identified underlying rare splicing defects mechanisms. The first mutation breaks a branch point sequence and the second alters a regulatory exonic splicing site. These splicing defects induce the skipping of exon 6 encoding the transmembrane domain of CD95. Our findings highlight the requirement of tight regulation of FAS exon 6 splicing for balanced alternative splicing and illustrate the importance of such studies in highly consanguineous populations. |
| Databáze: | OpenAIRE |
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