Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

TACIG
89122
Clinical References: 1. Mackay F, Ambrose C: The TNF family members BAFF and APRIL: the
growing complexity. Cytokine Growth Factor Rev 2003;14:311-324 2. Mackay F, Schneider P, Rennert
P, Browning J: BAFF and APRIL: a tutorial on B cell survival. Ann Rev Immunol 2003;21:231-264 3.
Castigli E, Geha RS: Molecular basis of common variable immunodeficiency. J Allergy Clin Immunol
2006;117:740-746 4. Castigli E, Wilson S, Garibyan L, et al: Reexamining the role of TACI coding
variants in common variable immunodeficiency and selective IgA deficiency. Nat Genet
2007;39(4):429-431 5. Salzar U, Chapel HM, Webster ADB, et al: Mutations in TNFRSF13B encoding
TACI are associated with common variable immunodeficiency in humans. Nat Genet 2005;37(8):820-828
6. Castigli E, Wilson SA, Garibyan L, et al: TACI is mutant in common variable immunodeficiency and
IgA deficiency. Nat Genet 2005;37(8):829-834 7. Scharenberg AM, Hannibal MC, Torgerson T, et al:
Common variable immunodeficiency overview. Gene Reviews 2006, Posted July 5, 2006
http://www.genetests.org/profiles/cvid
Transmembrane Activator and CAML Interactor (TACI) Gene,
Known Mutation Analysis
Clinical Information: Transmembrane activator and CAML interactor (TACI) is a member of the
tumor-necrosis factor (TNF)-like receptor family, a group of receptors that regulate both survival and
apoptosis of immune cells.(1) TACI is expressed on the surface of resting B cells and activated T cells,
but not resting T cells. TACI interacts with 2 ligands-BAFF (B-cell activating factor), also known as
BLys (B-lymphocyte stimulator), which belongs to the TNF family, and APRIL (a proliferation-inducing
ligand). The ligands for TACI are expressed on macrophages, monocytes, and dendritic cells.(1) TACI
regulates isotype class-switching of immunoglobulins and also is involved in the antibody response to
T-independent antigens.(2) TACI is encoded by the TACI gene (official symbol, TNFRSF13B). The
human TACI gene locus is located on the short arm of chromosome 17, which is a common target for
mutation and rearrangement.(2) The TACI gene consists of 5 exons spanning approximately 35 kb
(including 1002 bp upstream of the 5' untranslated region [UTR] and 1024 bp downstream of the 3' UTR).
The mRNA length is 1377 bp, encoding for a 294-amino acid protein with a molecular weight of 32.34
kD. Six mutations (D68X [also called L69fsX11], C104R, S144X, A181E, S194X, and R202H) were
identified in the TACI gene in the original reports.(3,4) Of these 6 mutations, 4 (D68X, C104R, A181E,
and R202H) have been shown to be statistically significant in common variable immunodeficiency
(CVID) and selective IgA deficiency (sIgAD) patients, when compared to controls.(5) Several other
mutations have been reported, but none of these appear to be statistically significant when compared to
controls.(5) Two other mutations, P251L and V220A, are considered to be rare polymorphisms as they are
present in both controls and patients.(3-5) The TACI mutations described so far are nonsense, missense,
or frameshift (due to the insertion of a single extra nucleotide) mutations, all of which can be detected by
gene sequencing. No large deletions or duplications have been reported for this gene at this time. TACI
mutations account for 8% to 15% of CVID cases depending on the study population and are sporadic in
the majority of cases. The familial TACI mutations can be inherited in either an autosomal dominant or
autosomal recessive fashion. There also appears to be variable penetrance in the familial TACI
mutations.(7) TACI mutations appear to be strongly associated with lymphoproliferative diseases such as
splenomegaly or tonsillar hypertrophy. Autoimmune thyroiditis is observed in 15% of TACI
mutation-positive CVID cases. The incomplete penetrance seen for TACI mutations indicates that a
mutation can be present, but the individual does not develop the disease phenotype. The known TACI
mutations appear, in most cases, to be associated with normal protein expression with aberrant or absent
functional activity and require gene sequencing analysis to confirm the presence of the mutation as well as
correlation with the clinical phenotype.
Useful For: Identifying the presence of a TACI mutation in a symptomatic patient when the mutation
has been identified in an affected family member
Interpretation: An interpretive report will be provided that describes the presence or absence of the
previously identified mutation(s), and their potential clinical significance. Variants of unknown clinical
significance within the specific exon being evaluated also will be documented in the report.
Reference Values:
An interpretive report will be provided.
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