The Invitae Thrombocytopenia-Absent Radius Syndrome Test analyzes the RBM8A gene that is associated with thrombocytopenia-absent radius (TAR) syndrome and is the commonly deleted gene in the 1q21.1 microdeletion syndrome. TAR syndrome is characterized by bilateral absence of the radii (thumbs remain present) and transient thrombocytopenia.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.
TAR syndrome is a congenital malformation disorder characterized by bilateral absence of the radii (thumbs remain present) and transient thrombocytopenia. Thrombocytopenia is usually congenital or develops in the first few weeks of life, and often decreases with age. There is a risk of gastrointestinal and intra-cerebral bleeding in the first few years of life. Intolerance to cow’s milk is common and may exacerbate thrombocytopenia. Intellect is usually normal. Other abnormalities include additional skeletal anomalies of the upper and lower limbs, characteristic facial features, cardiac anomalies and genitourinary anomalies. TAR is most often caused by the loss of the many genes within chromosome 1q21.1, including RBM8A and more rarely by pathogenic sequence variants in RBM8A.
RBM8A is currently the only gene known to cause autosomal recessive TAR syndrome. Most individuals with TAR syndrome have at least a 200-kb contiguous gene deletion including the RBM8A gene and a second pathogenic variant on the other allele.
TAR syndrome is inherited in an autosomal recessive manner.
Penetrance appears to be complete in individuals with two pathogenic variants in RBM8A. However, incomplete penetrance has been reported (PMID: 17236129).
The prevalence of TAR syndrome is estimated to be 1:200,000 to 1:100,000.
This test could be considered for individuals with bilateral absence of the radii with presence of both thumbs and thrombocytopenia.
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|
RBM8A: Analysis includes the non-coding variants NM_005105.4:c.-21G>A and c.67+32G>C.