title: Clinical, immunological and genetic findings of a large tunisian series of major histocompatibility complex class II deficiency patients.
abstract: BACKGROUND
  Major histocompatibility complex class II (MHC-II) expression deficiency is a combined primary immunodeficiency leading to the impairment of the cellular and humoral immune responses. A majority of affected patients belong to consanguineous families particularly from the Maghreb, where a founder effect for a highly frequent mutation (named c.338-25_338del26) in the RFXANK gene was reported. Herein, we report the largest single Maghrebian country series of MHC-II deficient patients.
  
  
  METHODS
  In Tunisia, among 551 PIDs diagnosed from 1993 to 2011, 54 had an MHC-II deficiency. The clinical features and immunological investigations were retrospectively analyzed in 34 children of them belonging to 28 kindred. The genetic study included the c.338-25_338del26 screening by the amplification of the affected region using polymerase chain reaction (PCR) followed by direct sequencing.
  
  
  RESULTS
  Consanguinity was present in 22 out of 28 families. Mean age at the first infection was 6.1 months. Chronic diarrhea with failure to thrive and pulmonary infections were the most common manifestations occurring in 26 and 28 patients respectively. The most specific laboratory findings were the defect of MHC-II (HLA-DR) expression in all patients. The c.338-25_338del26 mutation was identified in 25 of them.
  
  
  CONCLUSIONS
  In Maghrebian settings, pediatricians should definitely consider this diagnosis in the presence of an early onset of severe and recurrent infections of the respiratory and intestinal tracts, particularly protracted diarrhea with a failure to thrive. The founder effect for the c.338-25_338del26 mutation in the RFXANK gene is also confirmed, facilitating prenatal diagnosis as a preventive approach in the Tunisian affected families with severe forms, particularly in the context of limited access to bone marrow transplantation.
authors: Laboratoire de cyto-immunologie, LR11IPT02, Institut Pasteur de Tunis, Tunis, Tunisia.
authors: Imen
authors: I
authors: Ben-Mustapha
authors: Khaoula
authors: K
authors: Ben-Farhat
authors: Naouel
authors: N
authors: Guirat-Dhouib
authors: Emna
authors: E
authors: Dhemaied
authors: Beya
authors: B
authors: Larguèche
authors: Meriem
authors: M
authors: Ben-Ali
authors: Jalel
authors: J
authors: Chemli
authors: Jihène
authors: J
authors: Bouguila
authors: Lamia
authors: L
authors: Ben-Mansour
authors: Fethi
authors: F
authors: Mellouli
authors: Monia
authors: M
authors: Khemiri
authors: Mohamed
authors: M
authors: Béjaoui
authors: Mohamed-Ridha
authors: MR
authors: Barbouche
mesh_terms: D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D003967:Diarrhea / Q000209:etiology; D005183:Failure to Thrive / Q000209:etiology; D005260:Female; D018703:Founder Effect; D005820:Genetic Testing / Q000379:methods; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D007223:Infant; D008297:Male; D010375:Pedigree; D011296:Prenatal Diagnosis; D012141:Respiratory Tract Infections / Q000209:etiology; D012189:Retrospective Studies; D017384:Sequence Deletion / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014416:Tunisia
chemical_list: D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; C117892:RFXANK protein, human; D014157:Transcription Factors