1. Two siblings with PRKDC defect who presented with cutaneous granulomas and review of the literature
- Author
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Diclehan Orhan, Baran Erman, Ilhan Tezcan, Sibel Dogan, Can Akal, Deniz Cagdas Ayvaz, Saliha Esenboga, Kaan Boztug, and Betul Karaatmaca
- Subjects
0301 basic medicine ,Histiocytosis, Non-Langerhans-Cell ,T cell ,Immunology ,DNA-Activated Protein Kinase ,medicine.disease_cause ,Skin Diseases ,Autoimmunity ,03 medical and health sciences ,Immune system ,Pneumonia, Bacterial ,Humans ,Immunologic Factors ,Immunology and Allergy ,Medicine ,Epigenetics ,Severe combined immunodeficiency ,Mutation ,Granuloma ,business.industry ,Siblings ,Hematopoietic Stem Cell Transplantation ,Infant, Newborn ,Immunoglobulins, Intravenous ,Infant ,Nuclear Proteins ,medicine.disease ,Phenotype ,Transplantation ,030104 developmental biology ,medicine.anatomical_structure ,Child, Preschool ,Female ,Severe Combined Immunodeficiency ,business - Abstract
V(D)J recombination, during which recognition and repair of broken DNA chains are accomplished by non-homologous end joining pathway, is a critical process in B and T cell development.Null mutations of each enzyme or protein of this pathway result in T- B- NK+ severe combined immunodeficiency whereas hypomorphic mutations result in atypical(leaky)severe combined immunodeficiency forms. We present two siblings with PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) mutation who presented with granulomatous skin lesions and recurrent lung infections. Primary immune deficiencies may initially present with skin findings. Disruption in central and peripheral B-cell tolerance and impaired intrathymic T-cell maturation,a central player in T-cell tolerance, have been identified as the mechanism of autoimmunity and granuloma seen in patients. The variation in clinical phenotypes of patients with PRKDC mutation suggests that additional factors such as modifying genes, epigenetic and environmental factors may affect the severity and clinical phenotype of the disease. Functional studies during the follow-up and evaluation before and after hematopoeitic stem cell transplantation will hopefully increase our knowledge about the autoimmune and inflammatory process of the disease spectrum.
- Published
- 2018