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

Am J Hum Genet. 1999 Jan;64(1):172-9. doi: 10.1086/302194.


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 analysis, 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 score [Z]=6.99), D10S556 (Z=5.40), and D10S206 (Z=3.24), with a maximum multipoint LOD score of 11.22 at the D10S1650 locus. Haplotype analysis of these 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 evidence for genetic heterogeneity of this condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child, Preschool
  • Chromosomes, Human, Pair 10*
  • Female
  • Genetic Heterogeneity*
  • Genetic Linkage*
  • Genetic Markers
  • Haplotypes
  • Histiocytosis, Non-Langerhans-Cell / genetics*
  • Humans
  • Infant
  • Lod Score
  • Male
  • Pedigree
  • Software


  • Genetic Markers