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Hermansky-Pudlak Syndrome Type 8 (HPS8) via the BLOC1S3 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9181 BLOC1S3 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9181BLOC1S381479 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.

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 and 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 BLOC1S3/(HPS8) (OMIM 609762) account for ~2% 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%, AP3B1/(HPS2) ~6%, HPS3 ~15%, HPS4 ~12%, HPS5 ~5%, HPS6 ~4%, and DTNBP1/(HPS7) ~1%. To date, the only documented variant in BLOC1S3 that causes HPS8 was reported in a large family with HPS; all were homozygous for c.448delC that results in a frameshift and premature protein termination (Morgan et al. Am J Hum Genet 78:160-166, 2006). This family displayed the primary features of HPS (i.e. hypopigmentation, impaired visual acuity, and platelet dysfunction), but a bleeding tendency was not apparent in some individuals, and no individuals were affected by granulomatous colitis or pulmonary fibrosis.

Clinical Sensitivity - Sequencing with CNV PGxome

HPS8 accounts for ~2% of documented HPS cases.

Testing Strategy

This test provides full coverage of all coding exons of the BLOC1S3 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 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 BLOC1S3.

Gene

Official Gene Symbol OMIM ID
BLOC1S3 609762
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hermansky-Pudlak Syndrome 8 614077

Related Tests

Name
Hermansky-Pudlak Syndrome Type 2 (HPS2) via the AP3B1 Gene
Hermansky-Pudlak Syndrome Type 9 (HPS9) via the BLOC1S6/PLDN Gene
Hermansky-Pudlak Syndrome via the HPS3 Gene, Exon 1 Deletion

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
  • 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
  • Morgan, N. V., et.al. (2006). "A germline mutation in BLOC1S3/reduced pigmentation causes a novel variant of Hermansky-Pudlak syndrome (HPS8)." Am J Hum Genet 78(1): 160-6. PubMed ID: 16385460
  • 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

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


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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.
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