Hermansky-Pudlak Syndrome Type 9 (HPS9) via the BLOC1S6/PLDN Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT Prenatal
8749 BLOC1S6$890 8147981479,81479 Add to Order

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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

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, homozygous for the c.232 C>T (Gln78Term) pathogenic variant in the BLOC1S6 / HPS9 / PLDN gene, have been reported to date (Cullinane et al. 2011; Badolato et al. 2012).

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).

Testing Strategy

This test provides full coverage of all coding exons of the BLOC1S6 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV

Pathogenic variants in the BLOC1S6 / PLDN gene have been reported in only two patients to date (Cullinane et al. 2011; Badolato et al. 612012).

Indications for Test

Patients with symptoms or family history of HPS, CHS, or Griscelli Syndrome, patients with any degree of hypopigmentation and 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 BLOC1S6.

Gene

Official Gene Symbol OMIM ID
BLOC1S6 604310
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hermansky-Pudlak Syndrome 9 AR 614171

Related Test

Name
Familial Hemophagocytic Lymphohistiocytosis (FHL) Panel

Citations

  • Anikster et al. 2001. PubMed ID: 11455388
  • Badolato et al. 2012. PubMed ID: 22461475
  • Cullinane AR, Curry JA, Carmona-Rivera C, Summers CG, Ciccone C, Cardillo ND, Dorward H, Hess RA, White JG, Adams D, Huizing M, Gahl WA. 2011. A BLOC-1 Mutation Screen Reveals that PLDN Is Mutated in Hermansky-Pudlak Syndrome Type 9. Am J Hum Genet 88: 778–787. PubMed ID: 21665000
  • 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
  • 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

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.

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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