This test analyzes 10 genes that are associated with Diamond-Blackfan anemia (DBA). Diamond-Blackfan anemia is a genetically heterogeneous condition characterized by anemia, congenital malformations, growth restriction, and an increased risk for leukemia and sarcoma.
Genetic testing of these genes 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 that is not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept DNA derived from skin or muscle, though deletion/duplication analysis is not guaranteed for DNA samples because the success rate varies based on sample quality. Please see our Specimen requirements page for more details.
GATA1 RPL11 RPL26 RPL35A RPL5 RPS10 RPS19 RPS24 RPS26 RPS7
GATA1 RPL11 RPL26 RPL35A RPL5 RPS10 RPS19 RPS24 RPS26 RPS7
These genes can also be ordered as part of a broader panel. Depending on the individual’s clinical and family history, this panel may be appropriate and can be ordered at no additional charge.
DBA is a congenital hematological condition that is characterized by macrocytic anemia, reticulocytopenia, and normocellular bone marrow with a deficiency of red cell precursors. While the phenotypic spectrum can be mild to severe, approximately 90% of individuals with DBA will have some hematological symptoms within the first year of life. Congenital malformations, including craniofacial, upper limb, heart and genitourinary malformations, are seen in roughly 50% of individuals. Growth retardation is seen in roughly 30% of individuals. There is also an increased risk of developing acute myeloid leukemia, myelodysplastic syndrome, and solid tumors, including osteogenic sarcoma. Individuals with the non-classic form may have mild or absent anemia, a later age of onset, congenital abnormalities, or short stature with normal erythropoiesis, or they may be phenotypically normal.
Pathogenic variants in these genes account for an estimated 55%–65% of individuals with DBA.
|Gene||Attribution to DBA|
DBA is inherited in an autosomal dominant pattern, except for GATA1-related DBA, which is inherited in an X-linked pattern.
Penetrance is incomplete.
The prevalence of DBA is estimated at 5–7 out of 1 million live births.
Testing for DBA should be considered in individuals with a personal and/or family history of:
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 is 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, but 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.
Recommendations for diagnosis and management of DBA were proposed at an international DBA clinical consensus conference:
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, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
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|