MHC-II Deficiency Among Egyptians: Novel Mutations and Unique Phenotypes
| Autor: | Andrea A. Mauracher, Sohilla Lotfy, Alia Eldash, Rabab El Hawary, Aisha Elmarsafy, Radwa Alkady, Jana Pachlopnik Schmid, Lennart Opitz, Dalia Abd Elaziz, Nermeen Galal, Jeannette Boutros, Safa Meshaal |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Genes MHC Class II CIITA Gene Regulatory Factor X Transcription Factors Consanguinity Gene mutation medicine.disease_cause 03 medical and health sciences 0302 clinical medicine medicine Humans Immunology and Allergy 030212 general & internal medicine Child Immunodeficiency Mutation Severe combined immunodeficiency business.industry Histocompatibility Antigens Class II Immunologic Deficiency Syndromes Genetic disorder Infant Nuclear Proteins medicine.disease DNA-Binding Proteins Phenotype 030228 respiratory system Child Preschool Immunology Trans-Activators Egypt Female business RFX5 Transcription Factors |
| Zdroj: | The Journal of Allergy and Clinical Immunology: In Practice. 7:856-863 |
| ISSN: | 2213-2198 |
| DOI: | 10.1016/j.jaip.2018.07.046 |
| Popis: | Background MHC class II deficiency leads to defective CD4+ T-cell function that results from impaired antigen presentation. A genetic disorder in 1 of 4 genes results in this syndrome that is associated with the clinical phenotype of combined immunodeficiency. Objective To describe the clinical, immunological, and molecular characteristics of 10 Egyptian patients from 9 different families having presented with MHC class II deficiency between 2012 and 2017. Methods An initial diagnosis based on the combination of clinical features and low HLA-DR expression by flow cytometry was confirmed by genetic analyses. Results Symptoms included failure to thrive (n = 9), persistent diarrhea (n = 5), and pneumonia (n = 8). Septicemia due to coagulase-negative staphylococci (n = 1) and Candida krusei (n = 1) was diagnosed. Nine patients orally received the live attenuated polio vaccine, of whom 3 developed acute flaccid paralysis thereafter. Nine patients received the BCG vaccine and none developed obvious signs of BCGitis. Four patients carried RFXANK gene mutations, 3 carried RFX5 gene mutations, 1 carried a CIITA gene mutation, and none carried RFXAP gene mutations. Six of the 7 detected mutations were previously unreported mutations: c.431T>C, c.247_250delTCAG, and c.600delG in the RFXANK gene; c.116+1G>A and c.715C>T in the RFX5 gene; and c.929delA in the CIITA gene. Conclusions Given that Egypt is a North African country with a high rate of consanguinity, MHC class II deficiency is not rare. However, the molecular defects differ from those reported in nearby countries. Early diagnosis must be based on suspicious clinical signs and laboratory diagnosis because the defect can be missed by T-cell receptor excision circles based on neonatal screening. |
| Databáze: | OpenAIRE |
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