MHC-II Deficiency Among Egyptians: Novel Mutations and Unique Phenotypes

Background MHC class IIdeficiency 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 IIdeficiency 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 failureto 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 paralysisthereafter. Nine patients received the BCG vaccineand none developed obvious signs of BCGitis. Four patients carried RFXANKgene mutations, 3 carried RFX5gene mutations, 1 carried a CIITAgene 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 RFXANKgene; c.116+1G>A and c.715C>T in the RFX5gene; and c.929delA in the CIITAgene. Conclusions Given that Egypt is a North African country with a high rate of consanguinity, MHC class IIdeficiency 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 circlesbased on neonatal screening.