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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|