Linkage of familial hemophagocytic lymphohistiocytosis to 10q21-22 and evidence for heterogeneity

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disorder characterized by the early onset of overwhelming activation of T lymphocytes and macrophages, invariably leading to death, in the absence of allogeneic bone marrow transplantation, Using genomewide genetic Linkage a nalysis, we analyzed a group of 17 families with FHL and mapped a locus for FHL to the proximal region of the long arm of chromosome 10. Ten families showed no recombination with three tightly linked markers, D10S1650 (LOD sc ore [Z]=6.99), D10S556 (Z=5.40), and D10S206 (Z= 3.24), with a maximum mult ipoint LOD score of 11.22 at the D10S1650 locus. Haplotype analysis of thes e 10 families allowed us to establish D10S206 and D10S1665 as the telomeric and the centromeric flanking markers, respectively, Heterogeneity analysis and haplotype inspection of the remaining families confirmed that in seven families FHL was not linked to the 10q21-22 region, thus providing evidenc e for genetic heterogeneity of this condition.