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Mucopolysaccharidosis Type IX via the HYAL1 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
8781 HYAL1 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8781HYAL181479 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

  • Jana Paderova, PhD

Clinical Features and Genetics

Clinical Features

The mucopolysaccharidoses (MPS) are a group of inherited disorders caused by defects in lysosomal enzymes responsible for degradation of glycosaminoglycans (GAGs). Each enzyme deficiency results in progressive storage of distinct GAGs in multiple organ systems and subsequent abnormalities. Although MPS share several symptoms, including physical and mental developmental abnormalities, they may differ even within the same enzyme deficiency. MPS are classified in seven groups on the basis of the clinical symptoms (Types I, II, III, IV, VI, VII, and IX). Defects in eleven different enzymes have been connected with the various MPS (Neufeld and Muenzer 2001).

MPS IX is caused by hyaluronidase deficiency and subsequent accumulation of lysosomal hyaluronan. Only two instances of the condition have been reported. The first case is the only affected daughter of a non-consanguineous family. She presented, at the age of 7.5 years, with a soft tissue mass over an ankle. Additional features appeared later and include recurrent infections and periarticular soft-tissue masses accompanied by episodes of painful swelling that resolved within a 3-day period. These episodes started toward the end of the first decade of life. Stature of this patient was short; while visceral and mental development were normal (Natowicz et al. 1996). More recently, MPS IX was described in three affected children from a consanguineous family. In this family, the clinical features are restricted to painful swelling of the knees and/or hips. MRI findings indicated inflammation of the synovial membrane of joints (synovitis) (Imundo et al. 2011).

MPS IX is an exceptionally rare disorder, with an estimated prevalence of less than 1 in 1,000,000 live births (Orphanet).

Genetics

MPS IX is inherited in an autosomal recessive manner. It is caused by defects in the HYAL1 gene. Only three pathogenic variants in HYAL1 have been reported to date. Two of these were identified in the patient reported by Natowicz et al. (1996). The first is a missense variant defined as c.1412G>A (p.Glu268Lys). The second consists of a complex rearrangement defined as c.1361del37ins14 and predicted to result in premature protein termination (Triggs-Raine et al. 1999). A homozygous single nucleotide deletion (c.104delT) that is predicted to result in a truncated protein was identified in the affected members of the recently reported consanguineous family (Imundo et al. 2011).

The HYAL1 gene encodes the hyaluronidase enzyme, which catalyzes the degradation of hyaluronan, one of the main glycosaminoglycans of the extracellular matrix.

Clinical Sensitivity - Sequencing with CNV PGxome

Unknown, but HYAL1 mutations appear to be a rare cause of MPS (ORPHANET).

So far, no gross deletions or duplications have been reported in HYAL1 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the HYAL1 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 suggestive of MPS, increased plasma hyaluronan concentration, and reduced or complete deficiency of hyaluronidase enzyme activity; and potential heterozygous carriers.

Gene

Official Gene Symbol OMIM ID
HYAL1 607071
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mucopolysaccharidosis Type IX AR 601492

Citations

  • Human Gene Mutation Database (Bio-base).
  • Imundo L, Leduc CA, Guha S, Brown M, Perino G, Gushulak L, Triggs-Raine B, Chung WK. 2011. A complete deficiency of Hyaluronoglucosaminidase 1 (HYAL1) presenting as familial juvenile idiopathic arthritis. J. Inherit. Metab. Dis. 34: 1013–1022. PubMed ID: 21559944
  • Natowicz MR, Short MP, Wang Y, Dickersin GR, Gebhardt MC, Rosenthal DI, Sims KB, Rosenberg AE. 1996. Clinical and biochemical manifestations of hyaluronidase deficiency. N. Engl. J. Med. 335: 1029–1033. PubMed ID: 8793927
  • Neufeld EF, Muenzer J. 2001. The Mucoploysaccharidoses. 136: 3421-3452.
  • Orphanet
  • Triggs-Raine B, Salo TJ, Zhang H, Wicklow BA, Natowicz MR. 1999. Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX. Proc Natl Acad Sci U S A 96: 6296–6300. PubMed ID: 10339581

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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