Founder effect for a 26-bp deletion in the RFXANK gene in North African major histocompatibility complex class II-deficient patients belonging to complementation group B.
Expression of major histocompatibility complex (MHC) class II genes is controlled at the transcriptional level by at least four trans-acting genes, CIITA, RFXANK, RFX5, and RFXAP. Defects in these regulatory genes result in the absence of MHC class II molecule expression and, thereby, cause a combined immunodeficiency. MHC class II deficiency is inherited as an autosomal recessive trait. Since the first description of the disease, about 70 patients from 50 families have been reported. Forty-three of these families have been classified into four complementation groups: A, B, C, and D. In the largest group, B, the majority of patients are of North African origin. In two of these patients, the same mutation in the RFXANK gene (752delG-25) was identified. We performed a mutation analysis in 20 additional patients belonging to complementation group B and detected the 752delG-25 mutation in 17. All of these patients are of North African origin. A founder effect for this mutation was documented, since all tested patients, except one, display a common haplotype spanning the RFXANK locus.
Wiszniewski
W
W
INSERM U 429, Institut National de la Santé et de la Recherche Médicale, Hopital des Enfants Malades, Paris, France.
Fondaneche
M C
MC
Lambert
N
N
Masternak
K
K
Picard
C
C
Notarangelo
L
L
Schwartz
K
K
Bal
J
J
Reith
W
W
Alcaide
C
C
de Saint Basile
G
G
Fischer
A
A
Lisowska-Grospierre
B
B
D000352:Africa, Northern / Q000208:ethnology; D001483:Base Sequence; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003241:Consanguinity; D004268:DNA-Binding Proteins; D005260:Female; D018703:Founder Effect; D005802:Genes, MHC Class II; D005816:Genetic Complementation Test; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C117892:RFXANK protein, human; D014157:Transcription Factors