This test analyzes RUNX1, a gene associated with familial platelet disorder with propensity to myeloid malignancy (FPD/AML). This is a highly variable, autosomal dominant condition that is characterized by a mild-to-moderate bleeding tendency due to platelet defects and, in some cases, thrombocytopenia.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle, though deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Sample requirements page for more details.
These genes can also be ordered as part of broader panels. Depending on the individual’s clinical and family history, one of these panels may be appropriate and can be ordered at no additional charge.
Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is characterized by early onset mild-to-moderate thrombocytopenia and a family history of MDS/AML. This condition is highly variable, even among affected individuals in the same family.
Not all carriers of a RUNX1 pathogenic variant have a platelet disorder or present with abnormal platelet aggregation studies—even those affected with MDS/AML. Bleeding and abnormal platelet aggregation are not necessary for a diagnosis of FPD/AML. Patients may present with MDS/AML at any age. The median age of onset is 33 years, with a wide range that extends from childhood into late adulthood. The risk of MDS/AML is 35%–40% in carriers of a pathogenic variant.
RUNX1 is the only known gene associated with FPD/AML.
FPD/AML is inherited in an autosomal dominant pattern.
The incidence of FPD/AML is unknown.
Testing for germline RUNX1 pathogenic variants is recommended for individuals with MDS or AML, with or without a history of low blood counts or bleeding disorders, who have:
If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type that has not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle, though deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Sample requirements page for more details.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|