DNA icon

Mucopolysaccharidosis Type II via the IDS 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
7711 IDS 81405 81405,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7711IDS81405 81405,81479 $990 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.

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

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 the stepwise 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. Seven clinically distinct types can be recognized (Types I, II, III, IV, VI, VII, and IX). Based on the biochemical and genetic defects, MPS III and IV are further divided in four and two subtypes, respectively. Deficiencies in eleven enzymes have been implicated in the various MPS (Neufeld and Muenzer 2001; Coutinho et al. 2012 ). See also the National MPS Society at www.mpssociety.org.

MPS II, also called Hunter syndrome, is an X-linked recessive disorder caused by deficiency in the lysosomal iduronate sulfatase and subsequent accumulation of dermatan sulfate and heparin sulfate in several organ systems, resulting in a wide range of symptoms. MPS II is characterized by a great heterogeneity in regard to age of onset, severity and clinical course. Symptoms usually begin between 18 months and 4 years of age. In the most severe cases, death occurs by the second decade of life as the result of cardio-respiratory complications. Patients with the attenuated form live into adulthood. Typical symptoms include coarse facial features, short stature, stiff joint, thick bones, skeletal deformities, claw-hand deformity, skin lesions, airway obstruction, hearing loss, hepatosplenomagaly, cardiomyopathy, learning difficulties, and neurological decline. In contrast to MPS I, there is no corneal clouding in MPS II (Neufeld and Muenzer 2001; Wraith et al. 2008; Scarpa 2011).

MPS II occurs in diverse ethnic and geographical populations, with an estimated prevalence of 0.6 in 100,000 male live births (Orphanet, www.orpha.net).

Although rare, affected female carriers have been reported (Tuschl et al. 2005; Guillén-Navarro et al. 2013).

Genetics

Defects in the IDS gene (which is located on the X chromosome) are responsible for iduronate sulfatase deficiency and subsequent development of MPS II (Mossman et al. 1983). More than 500 causative variants have been reported. Most types of variants have been detected, including de novo mutations in sporadic male patients (Froissart et al. 1998). Total or partial deletions of the IDS gene represent ~8% of the catalogued mutations; and complex rearrangements represent ~ 3% of the mutations (Human Gene Mutation Database).

Although heterozygous female carriers are usually asymptomatic, Hunter disease has been reported in rare female cases as the result of skewed X-chromosome inactivation alone (Sukegawa et al. 1998) or in combination with de novo mutations on the paternal chromosome, or as the result of a homozygous mutation that led to mildly affected, undiagnosed male patients in consanguineous families (Cudry et al. 2000).

There are no clear genotype-phenotype correlations because most pathogenic variants are private. In addition, point mutations may result in a wide range of phenotypes, with the same mutation leading to different phenotypes even among siblings (Vafiadaki et al. 1998). Nonetheless, large deletions, which account for about 17% of patients, appear to result in a severe phenotype (Wraith et al. 2008).

The IDS gene encodes iduronate sulfatase, which catalyzes the first step of the degradation of dermatan and heparan sulfates.

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the IDS gene, including small insertions or deletions and point mutations, were identified in about 80% of the alleles in patients biochemically proven to have MPS II. Large deletions and complex rearrangements were identified in the remaining ~20% alleles (Brusius-Facchin et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the IDS gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Confirmation of the diagnosis of MPS II in patients, including males and rare females (Tuschl et al. 2005) with clinical features and radiological findings suggestive of MPS such as increased urinary dermatan and heparin sulfate excretion, and reduced iduronate sulfatase; and identification of asymptomatic heterozygous female carriers.

Gene

Official Gene Symbol OMIM ID
IDS 300823
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mucopolysaccharidosis, MPS-II XL 309900

Citations

  • Brusius-Facchin AC, Schwartz IVD, Zimmer C, Ribeiro MG, Acosta AX, Horovitz D, Monlleó IL, Fontes MIB, Fett-Conte A, Sobrinho RPO, Duarte AR, Boy R, et al. 2014. Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin American patients. Mol. Genet. Metab. 111: 133–138. PubMed ID: 24125893
  • Coutinho MF, Lacerda L, Alves S. 2012. Glycosaminoglycan Storage Disorders: A Review. Biochemistry Research International 2012: 1–16. PubMed ID: 22013531
  • Cudry S, Tigaud I, Froissart R, Bonnet V, Maire I, Bozon D. 2000. MPS II in females: molecular basis of two different cases. J. Med. Genet. 37: E29. PubMed ID: 11015461
  • Froissart R, Maire I, Millat G, Cudry S, Birot AM, Bonnet V, Bouton O, Bozon D. 1998. Identification of iduronate sulfatase gene alterations in 70 unrelated Hunter patients. Clin. Genet. 53: 362–368. PubMed ID: 9660053
  • Guillén-Navarro E, Domingo-Jiménez MR, Alcalde-Martín C, Cancho-Candela R, Couce ML, Galán-Gómez E, Alonso-Luengo O. 2013. Clinical manifestations in female carriers of mucopolysaccharidosis type II: a spanish cross-sectional study. Orphanet J Rare Dis 8: 92. PubMed ID: 23800320
  • Human Gene Mutation Database (Bio-base).
  • Mossman J, Blunt S, Stephens R, Jones EE, Pembrey M. 1983. Hunter’s disease in a girl: association with X:5 chromosomal translocation disrupting the Hunter gene. Arch Dis Child 58: 911–915. PubMed ID: 6418082
  • Neufeld EF, Muenzer J. 2001. The Mucoploysaccharidoses. 136: 3421-3452.
  • Orphanet
  • Scarpa M. 2011. Mucopolysaccharidosis Type II. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301451
  • Sukegawa K, Matsuzaki T, Fukuda S, Masuno M, Fukao T, Kokuryu M, Iwata S, Tomatsu S, Orii T, Kondo N. 1998. Brother/sister siblings affected with Hunter disease: evidence for skewed X chromosome inactivation. Clin. Genet. 53: 96–101. PubMed ID: 9611068
  • Tuschl K, Gal A, Paschke E, Kircher S, Bodamer OA. 2005. Mucopolysaccharidosis type II in females: case report and review of literature. Pediatr. Neurol. 32: 270–272. PubMed ID: 15797184
  • Vafiadaki E, Cooper A, Heptinstall L, Hatton C, Thornley M, Wraith J. 1998. Mutation analysis in 57 unrelated patients with MPS II (Hunter’s disease). Arch Dis Child 79: 237–241. PubMed ID: 9875019
  • Wraith JE, Beck M, Giugliani R, Clarke J, Martin R, Muenzer J, HOS Investigators. 2008. Initial report from the Hunter Outcome Survey. Genet. Med. 10: 508–516. PubMed ID: 18580692
  • Wraith JE, Scarpa M, Beck M, Bodamer OA, Meirleir L De, Guffon N, Meldgaard Lund A, Malm G, Ploeg AT Van der, Zeman J. 2008. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur. J. Pediatr. 167: 267–277. PubMed ID: 18038146

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

loading Loading... ×

ORDER OPTIONS

An error has occurred while calculating the price. Please try again or contact us for assistance.

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.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
×
Copy Text to Clipboard
×