Leukocyte Adhesion Deficiency Type 2 (LADII) via the SLC35C1 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
9121 | SLC35C1 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
The Sanger Sequencing method for this test is NY State approved.
For Sanger Sequencing click here.Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics 
Clinical Features
Leukocyte adhesion deficiency (LAD) is characterized by the inability of leukocytes, particularly neutrophils, to adhere to sites of inflammation in response to bacterial-derived attractants, cytokines, and other host-derived signals. Consequently, patients with LAD suffer from recurrent, severe infections. LAD is a consequence of defective adhesion molecule function: LADI (OMIM 116920) and LADIII (OMIM 612840) from defective integrin function, and LADII (OMIM 266265) from defective selectin function (Wild et al. Cells Tissues Organs 172:161-173, 2002). LADII (aka congenital disorder of glycosylation IIc) belongs to a group of hereditary carbohydrate-deficient glycoprotein syndromes (CDGS) characterized by impaired glycosylation of newly synthesized glycoproteins. A systemic defect in fucose metabolism results in the loss of fucosylated selectin ligands that under normal conditions are expressed on neutrophils and are required for tethering to the endothelium during the immune response (Tyrrell et al. PNAS 88:10372 -10376, 1991). Patients with LADII have high neutrophil counts and normal opsonophagocytic and bactericidal activity; however, neutrophil migration is defective (Etzioni et al. N Engl J Med 327:1789-1792, 1992). The clinical course of deficient neutrophil adhesion is milder in LADII than in other forms of LAD; however, LADII patients present other abnormal features including severe mental and growth retardation and distinctive facial features, and they lack the Lewis blood group antigens Lea and Leb as well as the H blood group antigen, a fucosylated carbohydrate (Bombay phenotype; Etzioni et al. 1992). Thus, fucosylated glycoconjugates appear to be important for mental and psychomotor development as well as the immune response. There is some evidence that oral doses of fucose can reverse some effects of LADII (Marquardt et al. Blood 94:3976-3985, 1999), but such treatment may not be effective in all LADII patients (Etzioni et al. Blood 95:3641-3643, 2000).
Genetics
LADII is caused by recessive variants in the SLC35C1 gene which encodes a GDP-fucose transporter located on Golgi vesicles (Lühn et al. Nat Genet 28:69-72, 2001; Lübke et al. Nat Genet 28:73-76, 2001). To date, 4 missense variants and one small deletion represent the only causative variants reported in the SLC35C1 gene (Lübke et al. 2001; Gazit et al. J Clin Immunol 30:308-313, 2010; Helmus et al. Blood 107:3959, 2006; van de Vivjer et al. Blood Cells Mol Dis 48:53, 2012; Hidalgo et al. Blood 101:1705).
Clinical Sensitivity - Sequencing with CNV PGxome
LADII is a rare form of LAD that represents a small fraction of all cases.
Testing Strategy
This test provides full coverage of all coding exons of the SLC35C1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).
Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).
Indications for Test
Patients with recurrent infections and high neutrophil counts, and patients with the Bombay blood type. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC35C1.
Patients with recurrent infections and high neutrophil counts, and patients with the Bombay blood type. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC35C1.
Gene
Official Gene Symbol | OMIM ID |
---|---|
SLC35C1 | 605881 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Congenital Disorder Of Glycosylation Type 2C | 266265 |
Citations 
- Etzioni, A., et.al. (1992). "Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency." N Engl J Med 327(25): 1789-92. PubMed ID: 1279426
- Etzioni, A., Tonetti, M. (2000). "Fucose supplementation in leukocyte adhesion deficiency type II." Blood 95(11): 3641-3. PubMed ID: 10877554
- Gazit, Y., et.al. (2010). "Leukocyte adhesion deficiency type II: long-term follow-up and review of the literature." J Clin Immunol 30(2): 308-13. PubMed ID: 20099014
- Helmus, Y. et al. (2006). "Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter". Blood 107(10):3959-66. PubMed ID: 16455955
- Hidalgo, A. et al. (2003). "Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene". Blood 101(5):1705-12. PubMed ID: 12406889
- Lubke, T., et.al. (2001). "Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency." Nat Genet 28(1): 73-6. PubMed ID: 11326280
- Luhn, K., et.al. (2001). "The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter." Nat Genet 28(1): 69-72. PubMed ID: 11326279
- Marquardt, T., et.al. (1999). "Correction of leukocyte adhesion deficiency type II with oral fucose." Blood 94(12): 3976-85. PubMed ID: 10590041
- Tyrrell, D., et.al. (1991). "Structural requirements for the carbohydrate ligand of E-selectin." Proc Natl Acad Sci U S A 88(22): 10372-6. PubMed ID: 1719556
- van de Vijver, E. et al. (2012). "Hematologically important mutations: leukocyte adhesion deficiency (first update)". Blood Cells Mol Dis 48(1):53-61.
PubMed ID: 22134107 - Wild, M. K., et.al. (2002). "Leukocyte adhesion deficiency II: therapy and genetic defect." Cells Tissues Organs 172(3): 161-73. PubMed ID: 12476046
Ordering/Specimens 
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
STAT and Prenatal Test Options are not available with Patient Plus.
No Additional Test Options are available for this test.