Thrombocythemia 2
A number sign (#) is used with this entry because thrombocythemia-2 (THCYT2) is caused by heterozygous germline or somatic mutation in the MPL gene (159530) on chromosome 1p34.
For a general phenotypic description and a discussion of genetic heterogeneity of thrombocythemia, see THCYT1 (187950).
Clinical FeaturesDing et al. (2004) reported a 3-generation Japanese family in which 8 of 16 members had thrombocythemia, with a platelet count more than 600 x 109/L. Bone marrow biopsies were normocellular and normoplastic, except for increased megakaryocytes.
InheritanceThe transmission pattern of thrombocythemia in the family reported by Ding et al. (2004) was consistent with autosomal dominant inheritance.
Molecular GeneticsGermline Mutation in the MPL Gene
In affected members of a Japanese family with autosomal dominant thrombocythemia, Ding et al. (2004) identified a heterozygous activating mutation in the MPL gene (159530.0010).
Moliterno et al. (2004) found that approximately 7% of African Americans are heterozygous for a single nucleotide substitution in the MPL gene, 1238G-T, which results in a lys39-to-asn substitution (K39N; 159530.0009). African Americans with the K39N polymorphism, which the authors designated MPL Baltimore, had a significantly higher platelet count than controls without the polymorphism (p less than 0.001) and reduced platelet protein MPL expression. Moliterno et al. (2004) concluded that K39N represents a functional MPL polymorphism and is associated with altered protein expression of the thrombopoietin receptor and a clinical phenotype of thrombocytosis. Although DNA was isolated from platelets or peripheral blood from most individuals in the study, K39N was also present in DNA obtained from buccal smears from 2 of the patients available for study.
Somatic Mutation in the MPL Gene
Pardanani et al. (2006) identified a somatic mutation in the MPL gene (W515L; 159530.0011) in 4 unrelated patients with thrombocythemia.