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Amegakaryocytic thrombocytopenia and radio-ulnar synostosis are associated with HOXA11 mutation

Nature Genetics volume 26, pages 397–398 (2000)Cite this article

Homeobox genes encode regulatory proteins that are central to bone morphogenesis as well as haematopoietic differentiation and proliferation4,5. Because HOXA10 and HOXA11 are involved in forearm morphogenesis, and HOXA10 is expressed in megakaryocytic bone marrow precursor cells, we focused our genetic evaluation on these genes.

The point mutation occurs in the third helix of the homeodomain, which is critical for DNA binding (Fig. 2b). This single-nucleotide deletion results in a translational frameshift followed by a premature stop, resulting in a truncated protein. It is similar to the mutation of HOXA13 identified in hand-foot-genital syndrome, in which an A→G transition changes a tryptophan to a stop codon in the third helix7. The phenotypic skeletal defect with synostosis in the distal extremity for HOXA13, and in the forearm for HOXA11, reflects the respective expression domains for each gene.

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Figure 1: Skeletal defect and pedigrees.
Figure 2: Molecular analysis of HOXA11.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Hematology/Oncology, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles School of Medicine, Los Angeles, California, USA

    Alexis A. Thompson & Long T. Nguyen

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  1. Alexis A. Thompson
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  2. Long T. Nguyen
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Correspondence to Alexis A. Thompson.

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Thompson, A., Nguyen, L. Amegakaryocytic thrombocytopenia and radio-ulnar synostosis are associated with HOXA11 mutation. Nat Genet 26, 397–398 (2000). https://doi.org/10.1038/82511

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