Hermansky-Pudlak Syndrome Type 2 (HPS2) via the AP3B1 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 4555 | AP3B1 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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
Hermansky-Pudlak syndrome (HPS) is characterized by tyrosinase-positive oculocutaneous albinism, significant reduction in visual acuity often complicated by nystagmus, and bleeding diathesis resulting in bruising and sporadic, prolonged bleeding (Hermansky and Pudlak. Blood 14:162-169, 1959). Hair color ranges from white to brown and, along with skin color, is typically a shade lighter than is seen in unaffected family members. HPS patients may develop granulomatous colitis, with onset usually in their teens, or pulmonary fibrosis, with onset typically in their thirties or forties (Gahl et al. N Engl J Med 338:1258-1264, 1998). Similar characteristics are found with the related Chediak-Higashi syndrome (CHS) (OMIM 214500). Both HPS and CHS are storage pool disorders. The cellular origin of disease is attributed to abnormal storage granules such as melanosomes, platelet-dense granules, and lysosomes. Granule cargo includes pigment proteins, signaling molecules, and enzymes. Defects in granule biogenesis, structure, or function affect myriad downstream events. Micrographs of platelets from HPS patients often reveal a striking lack of dense granules, whereas granulocytes of CHS patients contain giant, aberrant storage granules.
Genetics
HPS is an autosomal recessive disorder associated with the HPS1, AP3B1/(HPS2), HPS3, HPS4, HPS5, HPS6, DTNBP1/(HPS7), and BLOC1S3/(HPS8) genes. HPS is unusually common in Puerto Rico and is caused by unique variants in HPS1 and HPS3 (Santiago et al. J Invest Dermatol 126:85-90, 2006; Anikster et al. Nat Genet 28:376-380, 2001). In non-Puerto Ricans, variants in AP3B1 (OMIM 603401) account for ~6% of documented HPS cases (Oh et al. Am J Hum Genet 62:593-598, 1998), with the remaining cases being distributed as follows: HPS1 ~50%, HPS3 ~15%, HPS4 ~12%, HPS5 ~5%, HPS6 ~4%, DTNBP1/(HPS7) ~1%, and BLOC1S3/(HPS8) ~2%. Patients with HPS2 have variants in the AP3B1 gene that encodes the ß chain of the adaptor protein-3 (AP-3) complex. The AP-3 complex plays a role during the budding of vesicles from the trans Golgi network and endosomal compartments and is essential for proper intracellular protein sorting and vesiculation (Simpson et al. J Cell Biol 137:835-845, 1997). Patients with HPS2 are more likely than other HPS patients to develop congenital neutropenia and are thus more susceptible to infections (Jung et al. Blood 108:362-369, 2006). The cytotoxic T lymphocytes in HPS2 patients display impaired killing activity due to lytic granule abnormalities (Clark et al. Nat Immunol 4:1111-1120, 2003). It is worth noting that of all HPS subtypes, HPS2 most closely resembles CHS.
Clinical Sensitivity - Sequencing with CNV PG-Select
HPS2 accounts for ~6% of documented HPS cases among non-Puerto Ricans.
Testing Strategy
This test provides full coverage of all coding exons of the AP3B1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Patients with symptoms or family history of HPS, CHS, or Griscelli syndrome; patients with any degree of hypopigmentation or bleeding diathesis; and patients with morphologically abnormal granulocytes or platelets. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in AP3B1.
Patients with symptoms or family history of HPS, CHS, or Griscelli syndrome; patients with any degree of hypopigmentation or bleeding diathesis; and patients with morphologically abnormal granulocytes or platelets. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in AP3B1.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| AP3B1 | 603401 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Hermansky-Pudlak Syndrome 2 | AR | 608233 |
Related Tests
Citations
- Anikster Y, Huizing M, White J, Shevchenko YO, Fitzpatrick DL, Touchman JW, Compton JG, Bale SJ, Swank RT, Gahl WA, Toro JR. 2001. Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico. Nat. Genet. 28: 376–380. PubMed ID: 11455388
- Clark, R. H., et.al. (2003). "Adaptor protein 3-dependent microtubule-mediated movement of lytic granules to the immunological synapse." Nat Immunol 4(11): 1111-20. PubMed ID: 14566336
- Gahl WA, Brantly M, Kaiser-Kupfer MI, Iwata F, Hazelwood S, Shotelersuk V, Duffy LF, Kuehl EM, Troendle J, Bernardini I. 1998. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky–Pudlak syndrome). New England Journal of Medicine 338: 1258–1265. PubMed ID: 9562579
- Hermansky F, Pudlak P. 1959. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies. Blood 14: 162–169. PubMed ID: 13618373
- Jung J. 2006. Identification of a homozygous deletion in the AP3B1 gene causing Hermansky-Pudlak syndrome, type 2. Blood 108: 362–369. PubMed ID: 16537806
- Oh, J., et.al. (1998). "Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity." Am J Hum Genet 62(3): 593-8. PubMed ID: 9497254
- Santiago Borrero PJ, Rodriguez-Perez Y, Renta JY, Izquierdo NJ, Fierro L del, Munoz D, Molina NL, Ramirez S, Pagan-Mercado G, Ortiz I, Rivera-Caragol E, Spritz RA, et al. 2006. Genetic Testing for Oculocutaneous Albinism Type 1 and 2 and Hermansky-Pudlak Syndrome Type 1 and 3 Mutations in Puerto Rico. J Invest Dermatol 126: 85–90. PubMed ID: 16417222
- Simpson, F., et.al. (1997). "Characterization of the adaptor-related protein complex, AP-3." J Cell Biol 137(4): 835-45. PubMed ID: 9151686
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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ORDER OPTIONS
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