β-Mannosidase Deficiency via the MANBA 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
4351 MANBA 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4351MANBA81479 81479(x2) $890 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 backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

Clinical Features and Genetics

Clinical Features

β-Mannosidosis is a rare lysosomal storage disorder caused by defects in the enzyme β-Mannosidase. Defects in this enzyme lead to the accumulation of the disaccharide Man(β1→4)GlnNAc in lysosomes as well as its excretion in the urine of affected patients (Alkhayat et al. 1998; Bedilu et al. 2002). Very few patients have been reported in the literature and thus it is somewhat difficult to determine a cohesive clinical picture, but the most common features of β-Mannosidosis seem to be hearing loss, intellectual disability and developmental delay, behavior disturbances and susceptibility to respiratory infections. Less commonly reported features are facial dysmorphism, skeletal deformities, seizures, hypotonia, and skin involvement (such as angiokeratomas) (Alkhayat et al. 1998; Bedilu et al. 2002; Sedel et al. 2006; Molho-Pessach et al. 2007). A few patients have been reported with additional clinical features, such as Gilles de la Tourette Syndrome (Sedel et al. 2006), spinocerebellar ataxia (Labauge et al. 2009) and nystagmus (Yu et al. 2015), although it is not clear that these features are attributable to β-Mannosidase deficiency. Onset of symptoms has been reported to range from the neonatal period to adolescence (Bedilu e tal. 2002), and there seems to be a wide variability in severity of symptoms, even within families (Alkhayat et al. 1998). Many of the reported patients have survived to maturity (Bedilu e tal. 2002).

Genetics

β-Mannosidosis is an autosomal recessive disorder caused by defects in the enzyme β-Mannosidase, which is encoded by the MANBA gene located on chromosome 4 (at 4q24). To date, fewer than 20 pathogenic variants have been reported in the MANBA gene. The majority of reported variants have been nonsense, frameshift and splice variants that lead to premature protein termination, although about a third of reported variants are missense substitutions (Riise Stensland et al. 2008; Human Gene Mutation Database).

The β-Mannosidase enzyme is responsible for one of the last steps in the degradation of N-linked oligosaccharides of glycoproteins (Alkhayat et al. 1998). Deficiencies in this enzyme lead to defective cleavage of a β-Mannoside linkage, resulting in the accumulation of the disaccharide Man(β1→4)GlnNAc.

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity is difficult to estimate because only a small number of patients have been reported. Analytical sensitivity should be high because all variants reported are detectable by direct sequencing.

No large deletions or duplications have been reported in the MANBA gene (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the MANBA 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 accumulation of Man(β1→4)GlnNAc in lysosomes and/or the urine are good candidates for this test, as are those with clinical features consistent with β-Mannosidosis. Family members of patients known to have MANBA variants are also good candidates, and we will sequence the MANBA gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
MANBA 609489
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Beta-D-Mannosidosis AR 248510

Citations

  • Alkhayat A.H. et al. 1998. Human Molecular Genetics. 7: 75-83. PubMed ID: 9384606
  • Bedilu R. et al. 2002. Molecular Genetics and Metabolism. 77: 282-90. PubMed ID: 12468273
  • Human Gene Mutation Database (Bio-base).
  • Labauge P. et al. 2009. Clinical Neurology and Neurosurgery. 111: 109-10. PubMed ID: 18980795
  • Molho-Pessach V. et al. 2007. Journal of the American Academy of Dermatology. 57: 407-12. PubMed ID: 17420068
  • Riise Stensland H.M. et al. 2008. Molecular Genetics and Metabolism. 94: 476-80. PubMed ID: 18565776
  • Sedel F. et al. 2006. Archives of Neurology. 63: 129-31. PubMed ID: 16401745
  • Yu P. et al. 2015. Genetics in Medicine. 17: 971-9. PubMed ID: 25741867

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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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