Immune deficiency, autoimmune disease and intellectual disability: A pleiotropic disorder caused by biallelic variants in the TPP2 gene
| Autor: | Fabio Candotti, Claudia Poloni, Christophe Bonvin, Belinda Campos-Xavier, Jean-Louis Blouin, Athina Fouriki, Mathieu Quinodoz, Carlo Rivolta, Stéphanie Christen-Zaech, Orbicia Riccio, Armand Bottani, Michael Hofer, Andrea Superti-Furga, Camille Kumps, Maja Beck-Popovic, Virginie G. Peter, Mattia Rizzi, Raffaele Renella, Felicitas Bellutti Enders, Frossard Valérie, Federica Angelini, Isis Atallah, Sheila Unger |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Genetic counseling Human leukocyte antigen 030105 genetics & heredity Aminopeptidases Autoimmune Diseases Frameshift mutation Young Adult 03 medical and health sciences Immune system Amino acid homeostasis Intellectual disability Genetics medicine Humans Child Dipeptidyl-Peptidases and Tripeptidyl-Peptidases Frameshift Mutation Genetics (clinical) Immunodeficiency Autoimmune disease business.industry Serine Endopeptidases Immunologic Deficiency Syndromes Exons medicine.disease 030104 developmental biology Child Preschool Immunology Female business |
| Zdroj: | Clinical Genetics. 99:780-788 |
| ISSN: | 1399-0004 0009-9163 |
| Popis: | Four individuals from two families presented with a multisystemic condition of suspected genetic origin that was diagnosed only after genome analysis. The main phenotypic features were immune system dysregulation (severe immunodeficiency with autoimmunity) and intellectual disability. The four individuals were found to be homozygous for a 4.4 Kb deletion removing exons 20 to 23 (NM_003291.4) of the TPP2 gene, predicting a frameshift with premature termination of the protein. The deletion was located on a shared chromosome 13 haplotype indicating a Swiss founder mutation. Tripeptidyl peptidase 2 (TPP2) is a protease involved in HLA/antigen complex processing and amino acid homeostasis. Biallelic variants in TPP2 have been described in ten individuals with variable features including immune deficiency, autoimmune cytopenias, and intellectual disability or chronic sterile brain inflammation mimicking multiple sclerosis. Our observations further delineate this severe condition not yet included in the OMIM catalog. Timely recognition of TPP2 deficiency is crucial since (1) immune surveillance is needed and hematopoietic stem cell transplantation may be necessary, and (2) for provision of genetic counseling. Additionally, enzyme replacement therapy, as already established for TPP1 deficiency, might be an option in the future. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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