Chediak-Higashi Syndrome (CHS) via the LYST 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
3171 LYST 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3171LYST81479 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

Chediak-Higashi syndrome (CHS) (OMIM 214500) is characterized by partial albinism, bleeding diathesis, nystagmus, neutropenia, and other immunodeficiencies causing recurrent infections (Chediak. Rev Hematol 7:362-367, 1952; Higashi Tohoku. J Exp Med 59:315-332, 1954; Donohue and Bain. Pediatrics 20:416-430, 1957). Bleeding diathesis results from deficient platelet-dense granules that, in unaffected individuals, normally harbor signaling molecules essential for thrombosis. The CHS phenotype is similar to that of Hermansky Pudlak syndrome (HPS) (OMIM 203300), and both diseases are related to storage granule abnormalities. Blood smears and biopsies from CHS patients show giant inclusion bodies in granulocytes and cells from other tissues including skin and muscle (Introne et al. Mol Genet Metab 68:283-303, 1999). Most patients present symptoms in early childhood. Rarely, a patient may exhibit an intermediate adolescent CHS phenotype. In all forms of CHS, patients develop neurologic deficiencies including decreased cognitive ability, balance abnormalities, tremors, and other motor and sensory neuropathies (Tardieu et al. Blood 106:40-42, 2005). Approximately 85% of patients develop an accelerated phase of the disease known as hemophagocytic lymphohistiocytosis and characterized by hepatosplenomegaly, fever, jaundice, pancytopenia, and attenuated NK cell function (Blume and Wolff. Medicine (Baltimore) 51:247-280, 1972; Henter et al. Pediatr Blood Cancer 48:124-131, 2007).

Genetics

Chediak-Higashi syndrome (CHS) is an autosomal recessive disorder associated with the LYST gene (OMIM 606897). The exact function of the LYST protein is unknown, however LYST interacts with SNARE proteins, which are key members of the intracellular membrane fusion apparatus in cells. LYST may function as an adapter protein that helps juxtapose fusing membranes (Tchernev. Mol Med 8:56-64, 2002). Variants in LYST account for ~70% of CHS cases. Approximately 50 causative variants have been identified throughout the LYST gene including missense and nonsense variants, and small insertions and deletions. Studies show that patients with severe childhood CHS typically have functionally null mutant LYST alleles. In contrast, patients with adolescent and adult forms of CHS typically harbor missense variants resulting in LYST polypeptides that likely retain some functionality (Karim et al. Am J Med Genet 108:16-22, 2002; Westbroek et al. J Invest Dermatol 127:2674-2677, 2007; Zarzour. Mol Genet Metab 85:125-132, 2005).

Clinical Sensitivity - Sequencing with CNV PG-Select

Causative variants in the LYST gene have been found in ~ 70% of CHS cases.

Testing Strategy

This test provides full coverage of all coding exons of the LYST 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 CHS, Hermansky Pudlak Syndrome, or Griscelli Syndrome; patients with any degree of hypopigmentation or bleeding diathesis; patients with morphologically abnormal granulocytes or platelets; and patients with hemophagocytic lymphohistiocytosis. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LYST.

Gene

Official Gene Symbol OMIM ID
LYST 606897
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Chediak-Higashi Syndrome AR 214500

Related Tests

Name
Familial Hemophagocytic Lymphohistiocytosis (FHL) Panel
Severe Congenital Neutropenia Panel

Citations

  • Blume, R. S., Wolff, S. M. (1972). PubMed ID: 5064229
  • Chediak, M. M. (1952). PubMed ID: 13004553
  • Donohue, W. L., Bain, H. W. (1957). PubMed ID: 13465231
  • 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
  • Higashi, O. (1954). PubMed ID: 13169161
  • Introne, W., et.al. (1999). PubMed ID: 10527680
  • Karim, M. A., et.al. (2002). PubMed ID: 11857544
  • Tardieu, M., et.al. (2005). PubMed ID: 15790783
  • Tchernev VT, Mansfield TA, Giot L, Kumar AM, Nandabalan K, Li Y, Mishra VS, Detter JC, Rothberg JM, Wallace MR. 2002. The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins. Molecular Medicine 8: 56-64. PubMed ID: 11984006
  • Westbroek, W., et.al. (2007). PubMed ID: 17554367
  • Zarzour, W., et.al. (2005). PubMed ID: 15896657

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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