MHC class II deficiency: Report of a novel mutation and special review

Abstract

The MHC II deficiency is a rare autosomal recessive primary immunodeficiency syndrome with increased susceptibility to respiratory and gastrointestinal infections, failure to thrive and early mortality. This syndrome is caused by mutations in transcription regulators of the MHC II gene and results in development of blind lymphocytes due to the lack of indicatory MHC II molecules. Despite homogeneity of clinical manifestations of patients with MHC II deficiency, the genetic defects underlying this disease are heterogeneous. Herein, we report an Iranian patient with MHC II deficiency harbouring a novel mutation in RFXANK and novel misleading clinical features. He had ataxic gait and dysarthria from 30 months of age. Epidemiology, clinical and immunological features, therapeutic options and prognosis of patients with MHC II are reviewed in this paper.

MHC Class II Deficiency with Normal CD4+ T Cell Counts: A Case Report

“…In another study, Farrokhi and colleagues reported a 5-year-old Iranian boy with homozygous mutation in RFXANK gene on 19p12 as a substitution of G with A in TGG codon for W188 that resulted in a premature stop codon creation in exon 3 and caused recurrent fever, diarrhoea, failure to thrive, upper respiratory tract infection, and oral lesions since four months of age. 11 The reported mutation in this study is different from our presented case but was similarly in the RFXANK gene. As this mutation is considered serious and lethal and requires nonconservative treatments like HSCT.…”

“…As this mutation is considered serious and lethal and requires nonconservative treatments like HSCT. 6 Given these new gene mutations, this suggestion is proposed that 11 should pay more attention to this gene in Iran.…”

“…7,8 Few studies have been conducted on the genetic outcomes of Iranian patients 9,10 due to the lack of attention of the researcher. 11 Therefore, studies like this study focusing on the genetic principles of Iranian patients can help identify the most prevalent genetic mutations in Iran.…”

Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

“…The RFXAP protein consists of three regions, which are rich in acidic amino acids (DE), glutamine (Q), or basic amino acids (RK) reminiscent of a nuclear localization signal ( 12 ). Till date, only five different RFXAP gene mutations have been reported ( 2 ) with most of the mutations affecting the nuclear localization signal or DE regions. The RFXAP gene defect in exon 1 of our patients P1 and P2 also affects the nuclear localization signal and the mutation in intron 2 of patient P5 is expected to affect the formation of C-terminal domain, which is required for binding to the RFX complex ( 13 ).…”

“…About two-third of these patients have a North African descent (Algeria, Morocco, and Tunisia) ( 1 ) and belong to complementation group B. A high prevalence of group A deficiency is reported in the European countries ( 2 ). A defect in the factors that regulate the expression of MHC class II genes resulting in the absence or reduced expression of MHC class II molecules on the immune cells is thought to be the underlying cause of MHC class II deficiency ( 3 ).…”