Mapping of a gene for May-Hegglin anomaly to chromosome 22q

May-Hegglin anomaly (MHA) is a rare autosomal dominant platelet disorder characterized by the triad of giant platelets, thrombocytopenia and leukocyte inclusions. Both the molecular and the genetic defects responsible for this disorder remain unknown. In order to map the gene responsible for MHA, we performed a genome-wide linkage study using highly polymorphic short tandem repeat markers in a single Japanese MHA family. Significant linkage was obtained for the markers on the long arm of chromosome 22 (22q12.3–q13.2), with a maximum two-point lod score of 4.52 at a recombination fraction of 0.00 for the markers D22S1142 and D22S277. Haplotype analysis mapped a critical region for the disease locus to a 13.6-centimorgan region, between D22S280 and D22S272. The relative proximity of the platelet GPIbβ gene (22q11.2) to this region, as well as its involvement in an isolated giant platelet disorder, suggested a possible involvement of GPIbβ mutations in MHA. However, DNA-sequencing analysis in two patients revealed no abnormality in the sequence of the GPIbβ gene. This is the first report of linkage for MHA, and further analysis of this locus may lead to the identification of a gene the product of which regulates platelet and leukocyte morphology.