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Griscelli Syndrome-Type 2 (GS2) via the RAB27A 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
8987 RAB27A 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8987RAB27A81479 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

Griscelli syndrome (GS) is classified into three different subtypes, GS1 (OMIM 214450), GS2 (OMIM 607624), and GS3 (OMIM 609227), all of which are characterized by partial albinism, i.e. pigmentary dilution of the skin and hair. Patients with GS typically have large clumps of pigment irregularly distributed along hair shafts giving a silvery-gray appearance to hair color. GS1 is associated with severe primary neurologic defects while GS2 is associated with hemophagocytic lymphohistiocytosis (HLH / FHL) (see OMIM 267700). HLH is characterized by excessive, uncontrolled activation, and proliferation of T cells and macrophages that infiltrate tissues and cause organ failure. Common symptoms of HLH include: fever, hepatosplenomegaly, pancytopenia, attenuated or absent NK cell function, and hemophagocytosis (Henter et al. Pediatr Blood Cancer 48:124-131, 2007). Griscelli syndrome type 3 (GS3) is characterized by pigmentary dilution only. GS is commonly diagnosed between the ages of 4 months and 7 years.

Genetics

GS is an autosomal recessive disorder caused by variants in MYO5 (GS1), RAB27A (GS2), or MLPH (GS3). Variants in these genes affect melanosome trafficking and with GS1 and GS2, affect additional vesicular transport events. For example, RAB27A encodes a small GTPase (Rab27a) that is required for both anchoring melanosomes in melanocytes and for cytolytic granule secretion in T cells and NK cells (reviewed in Van Gele et al. Pigment Cell Melanoma Res 22:268-282, 2009). Thus, GS2 patients develop HLH and partial albinism. To date, about 30 causative variants in RAB27A have been identified, comprising missense variants, small and large deletions, and splice site variants (Meschede et al. Braz J Med Biol Res 41:839-848, 2008). Some missense variants have been shown to affect the Rab27a GTP-binding motif and protein-protein interaction domains (Menasche et al. Blood 101:2736-2742, 2003). Variants in RAB27A do not affect T cell or NK cell numbers but rather inhibit granule exocytosis in these cells similar to HLH / FHL genes. Rarely, variants in RAB27A result in immunological deficiencies without hemophagocytosis (Aksu et al. Am J Med Genet A 116A:329-333, 2003).

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity of this test is currently unknown.

Testing Strategy

This test provides full coverage of all coding exons of the RAB27A 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 clinical features of GS2, FHL, or FHL-related disorders and individuals with a family history of these disorders. FHL patients who test negative for variants in PRF1, UNC13D, STX11, and STXBP2 are also candidates. Conversely, GS2 patients who test negative for variants in RAB27A may be candidates for all or a portion of FHL, GS1, GS3, CHS, and HPS2 DNA testing. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RAB27A.

Gene

Official Gene Symbol OMIM ID
RAB27A 603868
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Griscelli Syndrome Type 2 AR 607624

Related Tests

Name
Familial Hemophagocytic Lymphohistiocytosis, X-linked Lymphoproliferative Disease via the SH2D1A Gene
Familial Hemophagocytic Lymphohistiocytosis, X-linked Lymphoproliferative Disease via the XIAP/BIRC4 Gene
Severe Congenital Neutropenia and Neutrophilia via the CSF3R Gene

Citations

  • Aksu, G., et.al. (2003). "Griscelli syndrome without hemophagocytosis in an eleven-year-old girl: expanding the phenotypic spectrum of Rab27A mutations in humans." Am J Med Genet A 116A(4): 329-33. PubMed ID: 12522785
  • Henter J-I, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G, for the Histiocyte Society. 2007. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatric Blood & Cancer 48: 124–131. PubMed ID: 16937360
  • Menasche, G., et.al. (2003). "Biochemical and functional characterization of Rab27a mutations occurring in Griscelli syndrome patients." Blood 101(7): 2736-42. PubMed ID: 12446441
  • Meschede, I. P., et.al. (2008). "Griscelli syndrome-type 2 in twin siblings: case report and update on RAB27A human mutations and gene structure." Braz J Med Biol Res 41(10): 839-48. PubMed ID: 19030707
  • Van Gele, M., et.al. (2009). "Griscelli syndrome: a model system to study vesicular trafficking." Pigment Cell Melanoma Res 22(3): 268-82. PubMed ID: 19243575

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)


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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