Immune dysregulation due to bi-allelic mutation of the actin remodeling protein DIAPH1
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Le résumé fourni par la source
Children with severe inflammatory diseases are challenging to diagnose and treat, and the etiology of disease often remains unexplained. Here we present DIAPH1 deficiency as an unexpected genetic finding in a child with fatal inflammatory bowel disease who also displayed complex neurological and developmental phenotypes. Bi-allelic mutations of DIAPH1 were first described in patients with a severe neurological phenotype including microcephaly, intellectual disability, seizures, and blindness. Recent findings have expanded the clinical phenotype of DIAPH1 deficiency to include severe susceptibility to infections, placing this monogenic disease amongst the etiologies of inborn errors of immunity. Immune phenotypes in DIAPH1 deficiency are largely driven aberrant lymphocyte activation, particularly the failure to form an effective immune synapse in T cells. We present the case of a child with a novel homozygous deletion in DIAPH1, leading to a premature truncation in the Lasso domain of the protein. Unlike other cases of DIAPH1 deficiency, this patient did not have seizures or lung infections. Her major immune-related clinical symptoms were inflammation and enteropathy, diarrhea and failure to thrive. This patient did not show T or B cell lymphopenia but did have dramatically reduced naïve CD4+ and CD8+ T cells, expanded CD4-CD8- T cells, and elevated IgE. Similar to other cases of DIAPH1 deficiency, this patient had non-hematological phenotypes including microcephaly, developmental delay, and impaired vision. This patient’s symptSoms of immune dysregulation were not successfully controlled and were ultimately fatal. This case expands the clinical spectrum of DIAPH1 deficiency and reveals that autoimmune or inflammatory enteropathy may be the most prominent immunological manifestation of disease.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Immune dysregulation due to bi-allelic mutation of the actin remodeling protein DIAPH1
- Date Crossref
- 15/07/2024
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Aster Medcity pays non établi dans la noticeÉtablissement de santé
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Apollo Gleneagles Hospitals pays non établi dans la noticeÉtablissement de santé
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Tata Main Hospital Department of Pediatrics pays non établi dans la noticeÉtablissement de santé
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Vanderbilt University Medical Center Department of Pathology Microbiology and Immunology pays non établi dans la noticeÉtablissement de santé
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Aster CMI Hospital Department of Pediatrics pays non établi dans la noticeÉtablissement de santé
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Department of Pediatric Hepatology pays non établi dans la noticeInstitution
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Vanderbilt Institute for Infection Vanderbilt Center for Immunobiology pays non établi dans la noticeStructure de recherche
Aster Medcity, Apollo Gleneagles Hospitals et Department of Pediatrics — Tata Main Hospital, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.