Autoimmune Lymphoproliferative Syndrome (ALPS Ia and ALPS 0) Related to Mutations in FAS Gene (TNFRSF6)
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About the Disorder | Indications | Specimen l Testing Methodology l Sensitivity l Turnaround Time l Cost l CPT Codes l Shipping l Results l Contact Us
About the Disorder
ALPS is a primary immunodeficiency disorder of defective FAS-mediated apoptosis (activation-induced cell death). Patients with ALPS develop chronic / recurrent lymphadenopathy and [hepato] splenomegaly, and autoimmune disease affecting blood cells and other tissues. There is a highly increased risk of lymphoma in ALPS patients.
Most patients with ALPS type Ia have a heterozygous mutation in the FAS gene, located at 10q24.1, which encodes the protein tumor necrosis factor receptor superfamily member 6 (TNFRSF6). In these patients, ALPS Ia is inherited as an autosomal dominant disorder. All known mutations in FAS result in defective FAS-mediated apoptosis. However, intracellular mutations (exons 7-9) are much more likely than extracellular mutations (exons 1-6) to be associated with a clinical ALPS phenotype. The presence of additional, unidentified genetic or environmental modifiers may be necessary to effect the development of the ALPS phenotype in individuals with FAS mutations.
Mutations in FAS are identified in approximately 70-75% of ALPS patients. Somatic mutations in FAS (limited to double negative T cells) have also been identified in a minority of ALPS patients. A small minority of ALPS patients have identified mutations in genes other than FAS, such as the FAS ligand (FASL) gene (ALPS type Ib), and caspase-10 (CASP10) gene (ALPS type II). Individuals with ALPS type III, which accounts for about 20%-25% of patients, do not have identified mutations in any of these genes.
Consistent laboratory abnormalities in ALPS patients include defective in vitro FAS-mediated apoptosis, the presence of double-negative (CD4/CD8-negative) T-cells, expressing the alpha / beta T-cell receptor, hyperimmunogobulinemia, cytokine alterations, autoantibodies, and elevated vitamin B12.
Clinical testing for ALPS should include:
- Full sequence analysis of FAS gene
- ALPS panel by flow cytometry
- FAS-apoptosis assay
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Indications
- Confirmation of diagnosis in a symptomatic individual
- Identification of at-risk individuals for future medical management
- Prenatal diagnosis of an at-risk fetus, after identification of a mutation in a proband (by previous arrangement only)
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Specimen
At least 3cc whole blood in purple top (EDTA) tube. Label tube with patient's name, birth date, and date of collection. Buccal swabs are required for analysis in patients who have undergone transplantation and may facilitate DNA isolation in patients undergoing chemotherapy or in individuals with leukopenia. Please call for a free buccal swab collection kit.
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Testing Methodology
PCR-based sequencing of the entire coding region and intron/exon boundaries of the FAS (TNFRSF6) gene.
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Sensivitity
Approximately 75% of patients with ALPS have a mutation in FAS. PCR-based sequencing detects the majority of mutations in the FAS gene. Gross deletions and rearrangements are present in less than 10% of patients with ALPS and are not detected with this methodology. Similarly, somatic mutations in double negative T cells have been reported in some patients with ALPS and are not detected with this test.
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Turnaround Time
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Cost
Please call 866-450-4198 for current pricing.
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CPT Codes
| 83890, 83898(x9), 83894(x9), 83891(x9), 83904(x18), 83912 |
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Shipping Instructions
Please enclose test requisition with sample. All information must be completed before sample can be processed. Place samples in Styrofoam mailer and ship at room temperature by overnight Federal Express to arrive Monday through Friday.
Ship to
Cytogenetics and Molecular Genetics Laboratories
3333 Burnet Avenue NRB 1042
Cincinnati, OH 45229
Phone 513-636-4474
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Results
Results will be reported to the referring physician or genetic counselor as specified on the requisition form.
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Contact Us
For additional inquiries, contact us:
Phone 513-636-4474
Fax 513-636-4373
Email moleculargenetics@cchmc.org
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