Localization of a gene for familial hemophagocytic lymphohistiocytosis at chromosome 9q21.3-22 by homozygosity mapping

Familial hemophagocytic lymphohistiocytosis (FHL), also known as familial e rythrophagocytic lymphohistiocytosis and familial histiocytic reticulosis, is a rare autosomal recessive disorder of early childhood characterized by excessive immune activation. Linkage of the disease gene to an similar to 7 .8-cM region between markers D9S1867 and D9S1790 at 9q21.3-22 was identifie d by homozygosity mapping in four inbred FHL families of Pakistani descent with a combined maximum multipoint LOD score of 6.05. This is the first gen etic locus to Poe described in FHL. However, homozygosity by descent across this interval could not be demonstrated in an additional affected kindred of Arab origin, whose maximum multipoint LOD score was -0.12. The combined sample revealed significant evidence for linkage to 9q markers (LOD score w ith heterogeneity, 5.00). Identification of the gene(s) involved in the pat hogenesis of FHL will contribute to an understanding of the control of T-ly mphocyte and macrophage activation, which is central to homeostasis in the immune system.