Macrothrombocytopenias with leukocyte inclusions are a set of hereditary clinical syndromes characterized by giant platelets and thrombocytopenia that include May-Hegglin anomaly (MHA), Fechtner syndrome, and Sebastian syndrome. The cause of these disorders is not known, but a gene causing MHA has recently been localized to chromosome 22. The PI has refined the mapping of this gene causing MHA in three families to a 6 cM, 1 Mb region of chr 22. The goal of the application is to identify the gene responsible for MHA and begin genetic investigation of related syndromes. Family ascertainment and characterization will be performed, as well as examination of candidate disease genes. When the causative gene is identified, biochemical and physiological analysis will be pursued including development of a murine model of the disease.
| Zhang, Yingfan; Conti, Mary Anne; Malide, Daniela et al. (2012) Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A. Blood 119:238-50 |
| Dong, Fan; Li, Sufeng; Pujol-Moix, Nuria et al. (2005) Genotype-phenotype correlation in MYH9-related thrombocytopenia. Br J Haematol 130:620-7 |
| Franke, Josef D; Dong, Fan; Rickoll, Wayne L et al. (2005) Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly. Blood 105:161-9 |
| Pujol-Moix, Nuria; Kelley, Michael J; Hernandez, Angel et al. (2004) Ultrastructural analysis of granulocyte inclusions in genetically confirmed MYH9-related disorders. Haematologica 89:330-7 |
