Familial platelet disorder with associated myeloid malignancy is an autosomal dominant disorder characterized by platelet defect and a propensity to myelodysplasia (MDS) and/or acute myeloid leukemia (AML). Fewer than 50% of individuals who inherit a RUNX1 mutation develop MDS/AML. The median incidence of MDS/AML among carriers of germline RUNX1 mutations is 35%. The RUNX1 protein encodes the alpha subunit of Core Binding Factor (CBF), a heterodimeric transcription factor that binds to the core element of many enhancers and promoters. RUNX1 is thought to be involved in the development of normal hematopoiesis. Sequence analysis of the entire RUNX1 gene is available on a clinical basis at the Medical Genetics Laboratories at Baylor College of Medicine.
Reasons For Referral:
- Confirmation of diagnosis in affected individuals
- Testing of known familial mutations
Testing Methodology:
PCR amplification of the exons contained in the RUNX1 gene coding region will be performed on patient genomic DNA. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.
Blood: EDTA (purple-top) tubes: Adults: 14 cc; Child: 6 cc; Infant: 2-3 cc
Turnaround Time: 4
weeks
Index: 83891, 83898x11, 83894, 83904x22, 83909x22, 83912
Known Familial Mutation: 83891, 83898, 83894, 83904x2, 83909x2, 83912
Forms:
>> Gene
Sequencing Requisition
References:
-
Song WJ, Sullivan MG, Legare RD, et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat. Genet. 1999; 23: 166-175.
- Owen CJ, Toze CL, Koochin A, Forrest DL, Smith CA, Stevens JM, Jackson SC, Poon MC, Sinclair GD, Leber B, Johnson PR, Macheta A, Yin JA, Barnett MJ, Lister TA, Fitzgibbon J. Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy (FPD/AML). Blood. Pre-published online August 21, 2008.
Test Codes:
Index: 6520
Known Familial Mutation: 6525
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