The Invitae Ulnar-Mammary Syndrome Test analyzes the TBX3 gene that is associated with ulnar-mammary syndrome (UMS), which is characterized by upper limb defects, mammary and apocrine gland hypoplasia, and genital abnormalities.
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.
Individuals with Holt-Oram syndrome (HOS), Townes-Brocks syndrome (TBS), and Duane-Radial Ray syndrome (DRRS) share phenotypic features with UMS. Given the significant overlap between these syndromes, as well as the difficulty in differentiating between these disorders, analyzing the TBX5, SALL1, and SALL4 genes, which are associated with HOS, TBS, and DRRS, respectively, may be appropriate. These tests may be included at no additional charge.
UMS is a congenital disorder characterized by upper limb defects, mammary and apocrine gland hypoplasia, and genital abnormalities. The upper limb defects can range from hypoplasia of the terminal phalanx of the 5th digit to complete absence of the ulna, reduction of the humerus, and absence of the digits. Upper limb abnormalities can be asymmetrical. Mammary and apocrine gland hypoplasia ranges from mild, with normal breast development, to severe with complete absence of breast development/inability to lactate, and absent axillary perspiration. Abnormal dentition, delayed puberty, short stature and heart defects have also been reported.
Due to the rarity of this condition, the percent of UMS attributed to pathogenic variants in TBX3 is currently unknown.
UMS is inherited in an autosomal dominant manner.
UMS is incompletely penetrant with high expressivity exhibiting marked inter and intra-familial variation.
The prevalence is not clearly established, but has been reported in approximately 117 individuals.
The main characteristics of a patient for whom this test would be appropriate for include:
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|