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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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4555 AP3B1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4555AP3B181479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Siwu Peng, PhD

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.

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

Name
Bleeding Disorders Panel
Familial Hemophagocytic Lymphohistiocytosis (FHL) Panel
Familial Hemophagocytic Lymphohistiocytosis, X-linked Lymphoproliferative Disease via the SH2D1A Gene
Familial Hemophagocytic Lymphohistiocytosis, X-linked Lymphoproliferative Disease via the XIAP/BIRC4 Gene
Hermansky-Pudlak Syndrome Type 8 (HPS8) via the BLOC1S3 Gene
Hermansky-Pudlak Syndrome Type 9 (HPS9) via the BLOC1S6/PLDN Gene
Hermansky-Pudlak Syndrome via the HPS3 Gene, Exon 1 Deletion
Severe Congenital Neutropenia and Neutrophilia via the CSF3R Gene
Severe Congenital Neutropenia Panel

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) 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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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