X-linked Lymphoproliferative Disease (XLP)
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About the Disorder | Indication | Specimen l Testing Methodology l Turnaround Time l Cost l CPT Codes l Shipping l Results l Contact Us
About the Disorder
The diagnosis of X-linked lymphoproliferative syndrome (XLP) should be suspected in males with fulminant Epstein-Barr virus (EBV) induced mononucleosis, which may be accompanied by hemophagocytosis. Affected males who survive the initial EBV infection develop a variable hypogammaglobulinemia and have a high risk of developing malignant lymphoma or other lymphoproliferative disease. Symptoms of XLP develop in some individuals without evidence of EBV infection.
Two genes have been specifically associated with XLP. SH2D1A, one of the causative genes of XLP, maps to Xq24-26. Mutations in SH2D1A account for at least 60% of cases of XLP. SH2D1A encodes a 128 amino acid protein known as SAP (SLAM associated protein), which is involved in lymphocyte activation signaling. The gene consists of four exons and three introns. Mutations involving all four exons have been identified. Large deletions account for approximately 25% of identified mutations in SH2D1A. NK cell function and SAP protein expression by flow cytometry are typically abnormal in individuals with mutations in SH2D1A.
A second gene for XLP, BIRC4, maps to Xq25, and is identified in an additional 20% of individuals with XLP. BIRC4 encodes a 497amino acid protein known as XIAP (X-linked inhibitor of apoptosis). Mutations in BIRC4 lead to defective apoptosis. The gene consists of six exons and five introns. Large deletions are expected to account for a significant number of mutations in BIRC4. NK expression is typically decreased in patients with BIRC4 mutations, while SAP protein expression is normal. At this time, there is no specific functional assay for XIAP. Splenomegaly was noted in the few patients reported to date with mutations in BIRC4. Splenomegaly is not a typical feature of XLP secondary to mutations in SH2D1A.
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Indications
- Diagnosis in a symptomatic individual
- Presymptomatic diagnosis in an at-risk individual
- Carrier identification in females with a family history
- Prenatal diagnosis of an at-risk fetus, after identification of a mutation in a proband (by prior 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 entire coding region and intron / exon boundaries of the SH2D1A and BIRC4 genes. Testing may be ordered sequentially or tandemly.
SAP protein expression by flow cytometry may be helpful in determining the most cost-effective order of tests. Please contact the Diagnostic Immunology Laboratory, 513-636-4769, for more information about SAP and NK-T testing.
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Sensitivity
The sensitivity of PCR-based sequence analysis is over 99% for the detection of nucleotide base changes, small deletions, and insertions in the regions analyzed. Mutations in regulatory regions or other untranslated regions are not detected by this test. Multiple exon deletions, large insertions and genetic recombinational events will not be identified in females using this test methodology. Large deletions account for 25% of mutations in SH2D1A in females and are expected to account for a significant proportion of mutations in BIRC4 as well.
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Turnaround Time
1 month
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Cost
Please call 1-866-450-4198 for current pricing or for any billing questions.
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CPT Codes
| SH2D1A |
83890, 83898 (x4), 83894 (x4), 83891 (x4), 83904 (x8), 83912 |
| BIRC4 |
83890, 83898 (x6), 83894 (x6), 83891 (X6), 83904 (x12), 83912 |
| Family specific study |
83890, 83898, 83894, 83891, 83904, 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
513-636-4474
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Results
Results will be reported to the referring physician or their designee 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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