Autozygosity Mapping, to Chromosome 11q25, of a Rare Autosomal Recessive Syndrome Causing Histiocytosis, Joint Contractures, and Sensorineural Deafness

We describe a highly consanguineous family, originating from Pakistan, displaying histiocytosis, joint contractures, and sensorineural deafness. The form of histiocytosis exhibited by this family does not fit readily into any of the recognized classes of this disease. It appears to represent a novel form of familial histiocytosis demonstrating autosomal recessive inheritance. Using autozygosity mapping, we have identified a homozygous region of ∼1 cM at chromosome 11q25, in affected individuals. A maximum two-point LOD score of 3.42 (recombination fraction θ = .00) was obtained with marker D11S968. This is the first genetic locus to be described that is involved in the molecular pathogenesis of histiocytosis.