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Mucopolysaccharidosis Type VII/Sly Syndrome via the GUSB 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
GUSB 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9941GUSB81479 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.


Genetic Counselors


  • 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 VII, also known as Sly syndrome, is caused by deficiency in lysosomal beta-glucuronidase and subsequent accumulation and excessive urinary excretion of dermatan sulfate, heparan sulfate, and chondroitin sulfate. Three major clinical forms (severe, intermediate and mild) have been described based on the age of onset, severity and disease course (Sly et al. 1973; Sewell et al. 1982).

The severe form is the most frequent presentation. It is characterized by prenatal onset, hydrops fetalis, and death in utero (Beaudet et al. 1975).

The intermediate form is characterized by variable age of onset, ranging from birth to childhood, and clinical severity. Clinical features include dysostosis multiplex, dysmorphic features, umbilical hernias, hepatosplenomegaly, skeletal abnormalities, short stature, vertebral deformation, hypotonia, neurological dysfunctions, mental retardation, and corneal clouding (Sewell et al. 1982).

The mild form is diagnosed during adolescence or adulthood. It presents with thoracic kyphosis and mild scoliosis, with survival into the fifth decade of life (Gitzelmann et al. 1978).

Beta-glucuronidase enzyme deficiency may be associated with increased risk for spontaneous abortions (Vervoort et al. 1996).

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


MPS VII is inherited in an autosomal recessive manner, and results from pathogenic variants in the GUSB gene (Fukuda et al. 1991). Over 50 variants, mostly missense, have been reported in patients from various ethnic and geographical populations. A few nonsense, small deletions and splicing variants were also reported (Tomatsu et al. 2009). No large deletions have been reported (Human Gene Mutation Database).

Most pathogenic variants are private, and the few variants detected in more than one family do not appear to be identical by descent (Vervoort et al. 1996).

Genotype-phenotype correlations are challenging for MPS VII due to the wide range of clinical heterogeneity, the low frequency of pathogenic variants, and the lack of longitudinal studies as the most frequent form is antinatal (Tomatsu et al. 2009).

The GUSB gene encodes the beta-glucuronidase enzyme, which is involved in the degradation of glucuronic acid-containing glycosaminoglycans.

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity is unknown as no studies assessing clinical sensitivity are known at this time. Using Sanger sequencing, pathogenic variants in the GUSB gene were identified in over 92% of the mutated alleles in patients biochemically proven to have MPS VII (Reviewed in Tomatsu et al. 2009).

No large deletions or duplications in the GUSB gene have been listed thus far (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the GUSB 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

Confirmation of the diagnosis of MPS VII in patients with clinical features and radiological findings suggestive of MPS, increased urinary excretion of dermatan sulfate, heparan sulfate, and chondroitin sulfate, and reduced beta-glucuronidase enzyme activity; and identification of asymptomatic heterozygous carriers.


Official Gene Symbol OMIM ID
GUSB 611499
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Mucopolysaccharidosis Type VII 253220


  • Beaudet AL, DiFerrante NM, Ferry GD, Nichols BL, Mullins CE. 1975. Variation in the phenotypic expression of beta-glucuronidase deficiency. J. Pediatr. 86: 388–394. PubMed ID: 803560
  • Coutinho MF, Lacerda L, Alves S. 2012. Glycosaminoglycan Storage Disorders: A Review. Biochemistry Research International 2012: 1–16. PubMed ID: 22013531
  • Fukuda S, Tomatsu S, Sukegawa K, Sasaki T, Yamada Y, Kuwahara T, Okamoto H, Ikedo Y, Yamaguchi S, Orii T. 1991. Molecular analysis of mucopolysaccharidosis type VII. J. Inherit. Metab. Dis. 14: 800–804. PubMed ID: 1779626
  • Gitzelmann R, Wiesmann UN, Spycher MA, Herschkowitz N, Giedion A. 1978. Unusually mild course of beta-glucuronidase deficiency in two brothers (mucopolysaccharidosis VII). Helv Paediatr Acta 33: 413–428. PubMed ID: 101485
  • Human Gene Mutation Database (Bio-base).
  • Human Gene Mutation Database.
  • National MPS Society
  • Neufeld EF, Muenzer J. 2001. The Mucoploysaccharidoses. 136: 3421-3452.
  • Orphanet
  • Sewell AC, Gehler J, Mittermaier G, Meyer E. 1982. Mucopolysaccharidosis type VII (beta-glucuronidase deficiency): a report of a new case and a survey of those in the literature. Clin. Genet. 21: 366–373. PubMed ID: 6813001
  • Sly WS, Quinton BA, McAlister WH, Rimoin DL. 1973. Beta glucuronidase deficiency: report of clinical, radiologic, and biochemical features of a new mucopolysaccharidosis. J. Pediatr. 82: 249–257. PubMed ID: 4265197
  • Tomatsu S, Montano AM, Dung VC, Grubb JH, Sly WS. 2009. Mutations and Polymorphisms in GUSB Gene in Mucopolysaccharidosis VII (Sly Syndrome). Hum Mutat 30: 511–519. PubMed ID: 19224584
  • Tomatsu S, Montano AM, Dung VC, Grubb JH, Sly WS. 2009. Mutations and Polymorphisms in GUSB Gene in Mucopolysaccharidosis VII (Sly Syndrome). Hum Mutat 30: 511–519. PubMed ID: 19224584
  • Vervoort R, Islam MR, Sly WS, Zabot MT, Kleijer WJ, Chabas A, Fensom A, Young EP, Liebaers I, Lissens W. 1996. Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII. Am J Hum Genet 58: 457–471. PubMed ID: 8644704
  • Vervoort R, Islam MR, Sly WS, Zabot MT, Kleijer WJ, Chabas A, Fensom A, Young EP, Liebaers I, Lissens W. 1996. Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII. Am J Hum Genet 58: 457–471. PubMed ID: 8644704


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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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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