title: Major histocompatibility complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients.
abstract: Inherited deficiency of major histocompatibility complex (MHC) class II molecules impairs antigen presentation to CD4(+) T cells and results in combined immunodeficiency (CID). Autosomal-recessive mutations in the RFXANK gene account for two-thirds of all cases of MHC class II deficiency. We describe here the genetic, clinical, and immunologic features of 35 patients from 30 unrelated kindreds from North Africa sharing the same RFXANK founder mutation, a 26-bp deletion called I5E6-25_I5E6 + 1), and date the founder event responsible for this mutation in this population to approximately 2250 years ago (95% confidence interval [CI]: 1750-3025 years). Ten of the 23 patients who underwent hematopoietic stem cell transplantation (HSCT) were cured, with the recovery of almost normal immune functions. Five of the patients from this cohort who did not undergo HSCT had a poor prognosis and eventually died (at ages of 1-17 years). However, 7 patients who did not undergo HSCT (at ages of 6-32 years) are still alive on Ig treatment and antibiotic prophylaxis. RFXANK deficiency is a severe, often fatal CID for which HSCT is the only curative treatment. However, some patients may survive for relatively long periods if multiple prophylactic measures are implemented.
authors: Pediatric Hematology-Immunology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital, France.
authors: Monia
authors: M
authors: Ouederni
authors: Quentin B
authors: QB
authors: Vincent
authors: Pierre
authors: P
authors: Frange
authors: Fabien
authors: F
authors: Touzot
authors: Sami
authors: S
authors: Scerra
authors: Mohamed
authors: M
authors: Bejaoui
authors: Aziz
authors: A
authors: Bousfiha
authors: Yves
authors: Y
authors: Levy
authors: Barbara
authors: B
authors: Lisowska-Grospierre
authors: Danielle
authors: D
authors: Canioni
authors: Julie
authors: J
authors: Bruneau
authors: Marianne
authors: M
authors: Debré
authors: Stéphane
authors: S
authors: Blanche
authors: Laurent
authors: L
authors: Abel
authors: Jean-Laurent
authors: JL
authors: Casanova
authors: Alain
authors: A
authors: Fischer
authors: Capucine
authors: C
authors: Picard
mesh_terms: D000293:Adolescent; D000352:Africa, Northern; D017951:Antigen Presentation / Q000235:genetics; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005260:Female; D018703:Founder Effect; D005767:Gastrointestinal Diseases / Q000209:etiology; D015870:Gene Expression; D005802:Genes, MHC Class II; D005808:Genes, Recessive; D018380:Hematopoietic Stem Cell Transplantation; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008107:Liver Diseases / Q000209:etiology; D008297:Male; D009154:Mutation; D012141:Respiratory Tract Infections / Q000209:etiology; D017384:Sequence Deletion; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C117892:RFXANK protein, human; D014157:Transcription Factors