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Hermansky-Pudlak Syndrome via the HPS3 Gene, Exon 1 Deletion

Summary and Pricing

Test Method

Targeted Deletion Testing via PCR
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
759 HPS3 81479 81479 $250 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
759HPS381479 81479(x1) $250 Order Options and Pricing

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 14 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.

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, bleeding diathesis, and significant reduction in visual acuity often characterized by nystagmus, reduced retinal and iris pigmentation, and foveal hypoplasia (Hermansky and Pudlak 1959). Hair and skin color are typically shades lighter than is seen in unaffected relatives. HPS patients may experience frequent epistaxis, easy bruising, and prolonged bleeding with injury or surgery. HPS patients may also develop immunodeficiencies, granulomatous colitis, with onset usually in their teens, and/or pulmonary fibrosis, with onset typically in their thirties or forties (Huizing et al. 2008; Gahl et al. 1998). Similar characteristics are found with the related Chediak-Higashi Syndrome (CHS). HPS and CHS are disorders of storage granules, e.g. melanosomes, platelet-dense granules, lysosomes, and lytic granules. A hallmark of HPS is a lack of platelet dense granules, as seen on electron micrographs (Witkop et al. 1987). CHS is distinguished by giant azurophilic granules in neutrophils, eosinophils, and other granulocytes (Introne et al. 1999).

Genetics

HPS is a genetically heterogeneous autosomal recessive disorder associated with the HPS1, AP3B1/(HPS2), HPS3, HPS4, HPS5, HPS6, DTNBP1/(HPS7), BLOC1S3/(HPS8), and BLOC1S6(HPS9) genes. HPS proteins belong to the BLOC (Biogenesis of Lysosome-related Organelle Complexes) groups of proteins that function during formation and/or trafficking of lysosme-related vesicles (Huizing et al. 2008). HPS is unusually common in Puerto Rico where regions of the country have an estimated carrier frequency as high as 1 in 21 (Wildenberg et al. 1995). Most affected Puerto Ricans harbor either a 16bp duplication in HPS1 or a 3.9kb deletion in HPS3 (Anikster et al. 2001; Santiago et al. 2006). In non-Puerto Ricans, HPS1 mutations account for ~50% of cases (Oh et al. 1998) with the remaining cases being distributed as follows: AP3B1/(HPS2) ~1%, HPS3 ~13%, HPS4 ~12%, HPS5 ~9%, HPS6 ~7%, DTNBP1/(HPS7) ~1%, BLOC1S3/(HPS8) ~1%, BLOC1S6 (HPS9) only two patients to date.

The severity of HPS varies among the subtypes and among family members having the same subtype, but some general genotype / phenotype correlations have emerged. Patients with HPS1 or HPS4 generally have more severe forms of HPS with more pronounced albinism, development of colitis (Hussain et al. 2006), a high occurrence of pulmonary fibrosis (Huizing et al. 2008), and accelerated ceroid lipfusin accumulation in lung, liver, bone marrow, kidney, and other cells (Huizing and Gahl 2002). The remaining subtypes are generally not associated with pulmonary fibrosis (Huizing et al. 2004), however, HPS2 and HPS9 have been associated with immunodeficiencies (Huizing et al. 2002; Badolato et al. 2012). Patients with HPS3 mutations tend to have milder symptoms than other HPS patients. Hypopigmentation and bleeding diathesis are mild and no significant granulomatous colitis or pulmonary fibrosis has been observed with HPS3. Most documented causative mutations in the HPS3 gene affect exon splicing; missense and nonsense mutations are rare.

Clinical Sensitivity - Targeted Deletion

This test is intended to detect the HPS3 exon 1 deletion found in Puerto Ricans; it will not detect any other sequence variant. In a cohort of 585 patients from 229 Puerto Rican families presenting with albinism, 39 patients were found  to be homozygous for the HPS3 exon 1 deletion (Santiago Borrero et al. 2006).  Sequencing the entire HPS3 coding region may be indicated in individuals who are clinically affected and have either one or no alleles with the exon 1 deletion. Complete HPS3 gene sequencing is available from PreventionGenetics (Test #4847).

Testing Strategy

Testing is accomplished by amplifying patient and control DNAs with PCR primers that flank or lie within the 3,904 bp deletion, essentially as described by Anikster et al (Anikster et al. 2001). This test permits the identification of patients with normal genotypes, patients who are homozygous for the deletion, and patients who are heterozygous carriers.

Indications for Test

Individuals of Puerto Ricans ancestry with symptoms or family history of HPS, patients with any degree of hypopigmentation and bleeding diathesis, and patients with morphologically abnormal granulocytes or platelets.

Gene

Official Gene Symbol OMIM ID
HPS3 606118
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hermansky-Pudlak Syndrome 3 AR 614072

Citations

  • Anikster et al. 2001. PubMed ID: 11455388
  • Badolato et al. 2012. PubMed ID: 22461475
  • Gahl et al. 1998. PubMed ID: 9562579
  • Hermansky and Pudlak. 1959. PubMed ID: 13618373
  • Huizing and Gahl. 2002. PubMed ID: 12125811
  • Huizing et al. 2002. PubMed ID: 11809908
  • Huizing et al. 2004. PubMed ID: 15296495
  • Huizing et al. 2008. PubMed ID: 18544035
  • Huizing M, Anikster Y, Fitzpatrick DL, Jeong AB, D’Souza M, Rausche M, Toro JR, Kaiser-Kupfer MI, White JG, Gahl WA. 2001. Hermansky-Pudlak Syndrome Type 3 in Ashkenazi Jews and Other Non-Puerto Rican Patients with Hypopigmentation and Platelet Storage-Pool Deficiency. Am J Hum Genet 69: 1022–1032. PubMed ID: 11590544
  • Hussain et al. 2006. PubMed ID: 16431308
  • Introne et al. 1999. PubMed ID: 10527680
  • Oh et al. 1998. PubMed ID: 9497254
  • Santiago Borrero et al. 2006. PubMed ID: 16417222
  • Wildenberg et al. 1995. PubMed ID: 7573033
  • Witkop et al. 1987. PubMed ID: 3120578

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.
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