Autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly) is linked to chromosome 22q12-13

Michael J. Kelley, William Jawien, Albert Lin, Karen Hoffmeister, Elizabeth W. Pugh, Kimberly F. Doheny, Jeannette F. Korczak

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly) is a rare autosomal dominant disorder characterized by thrombocytopenia, giant platelets, and Dohle body-like inclusions in leukocytes. To determine the genetic basis of this disorder, we performed a genome-wide screen for linkage in three families with May-Hegglin anomaly. For the pooled analysis of the three families, three markers on chromosome 22 had two-point logarithm-of-difference (lod) scores greater than 3, with a maximum lod score of 3.91 at a recombination fraction (θ) of 0.076 for marker D22S683. Within the largest family (MHA-1), the maximum lod score was 5.36 at θ = 0 at marker D22S445. Fine mapping of recombination events using eight adjacent markers indicated that the minimal disease region of family MHA-1 alone is in the ~26 cM region from D22S683 to the telomere. The maximum lod score for the three families combined was 5.84 at θ = 0 for marker IL2RB. With the assumption of locus homogeneity, haplotype analysis of family MHA-4 indicated the disease region is centromeric to marker D22S 1045. These data best support a minimal disease region from D22S683 to D22S1045, a span of about 1 Mb of DNA that contains 17 known genes and 4 predicted genes. Further analysis of this region will identify the genetic basis of May-Hegglin anomaly, facilitating subsequent characterization of the biochemical role of the disease gene in platelet formation.

Original languageEnglish (US)
Pages (from-to)557-564
Number of pages8
JournalHuman genetics
Issue number5
StatePublished - 2000

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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