A novel primary immunodeficiency with specific natural-killer cell deficiency maps to the centromeric region of chromosome 8.
We describe four children with a novel primary immunodeficiency consisting of specific natural-killer (NK) cell deficiency and susceptibility to viral diseases. One child developed an Epstein-Barr virus-driven lymphoproliferative disorder; two others developed severe respiratory illnesses of probable viral etiology. The four patients are related and belong to a large inbred kindred of Irish nomadic descent, which suggests autosomal recessive inheritance of this defect. A genomewide scan identified a single 12-Mb region on chromosome 8p11.23-q11.21 that was linked to this immunodeficiency (maximum LOD score 4.51). The mapping of the disease-causing genomic region paves the way for the identification of a novel pathway governing NK cell differentiation in humans.
Laboratory of Human Genetics of Infectious Diseases, University of Paris Rene Descartes-INSERM U550, Necker Medical School, Paris, France.
Celine
C
Eidenschenk
Jean
J
Dunne
Emmanuelle
E
Jouanguy
Claire
C
Fourlinnie
Laure
L
Gineau
Delphine
D
Bacq
Corrina
C
McMahon
Owen
O
Smith
Jean-Laurent
JL
Casanova
Laurent
L
Abel
Conleth
C
Feighery
D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D010375:Pedigree