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Molybdenum Cofactor Deficiency Type A via the MOCS1 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
8073 MOCS1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8073MOCS181479 81479,81479 $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.

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

  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Molybdenum cofactor deficiency type A is an inborn error in metabolism that results in defective synthesis of the molybdopterin cofactor required for the function of the sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase enzymes. Patients with molybdenum cofactor deficiency excrete elevated levels of sulfite, thiosulfate, S-sulfocysteine, taurine, xanthine, and hypoxanthine, while also exhibiting hypouricemia (Johnson and Duran 2014). Isolated deficiency of the xanthine dehydrogenase or aldehyde oxidase enzymes is a benign biochemical condition in most patients, while sulfite oxidase deficient patients present with a severe disease course. Clinical presentations in isolated sulfite oxidase deficiency and molybdenum cofactor deficiencies are almost indistinguishable (Mendel, 2009. PubMed ID: 19623604; Johnson and Duran, 2014).

Many times molybdenum cofactor deficiency will be misdiagnosed as infantile encephalopathy due to the brain anomalies and neurologic symptoms. Typically, presentation will occur early after birth with severe convulsions that are difficult to suppress (Reiss et al., 1998. PubMed ID: 9731530; Johnson and Duran, 2014). Pathological studies have shown there is marked neuronal loss and demyelination in the white matter accompanied by gliosis and diffuse spongiosis. Patients with milder clinical symptoms and later onset (6-15 months) have also been reported, although less than 10% of patients fall into this group. In many cases, an infection will trigger the first symptoms in later onset patients (Johnson and Duran, 2014). Patients with molybdenum cofactor deficiency or isolated sulfite oxidase deficiency also have dysmorphic features that include long face with puffy cheeks, widely spaced eyes, elongated palpebral fissures, thick lips, a long philtrum, and a small nose, which can resemble perinatal asphyxia. Patients also present with psychomotor retardation, ophthalmologic abnormalities such as lens dislocation, peripheral hypertonicity, and axial hypotonia (Johnson and Duran, 2014). Irreversible neurological damage occurs due to sulfite toxicity and/or sulfate deficiency, and most patients die during the neonatal period or early childhood (Reiss et al., 1998. PubMed ID: 9731530; Macaya et al., 2005. PubMed ID: 16429380).

Genetics

All molybdenum cofactor deficiencies are inherited in an autosomal recessive manner. Molybdenum cofactor deficiency type A is caused by pathogenic variants in the MOCS1 gene, which is located on chromosome 6 at 6p21.2. Reported pathogenic variants in this gene include missense and nonsense variants, splice variants, and small in-frame or frameshift deletions and duplications (Reiss and Johnson, 2003. PubMed ID: 12754701; Reiss and Hahnewald, 2011. PubMed ID: 21031595; Human Gene Mutation Database). One case of molybdenum cofactor deficiency due to a homozygous MOCS1 missense variant was shown to be a result of maternal uniparental isodisomy (Gümüs et al., 2010. PubMed ID: 20573177).

The MOCS1 gene encodes both the MOCS1A protein and the MOCS1AB fusion protein, which are generated via alternative splicing (Gray and Nicholls, 2000. PubMed ID: 10917590; Reiss, Johnson., 2003. PubMed ID: 12754701; Arenas et al., 2009. PubMed ID: 19544009; Reiss and Hahnewald, 2011. PubMed ID: 21031595). In the MOCS1AB fusion protein, only the MOCS1B portion is active (Arenas et al., 2009. PubMed ID: 19544009). Nomenclature of variants in the MOCS1 gene is complicated by the various alternative splicing mechanisms and multiple proteins encoded by this gene. Sequence variants in this gene are therefore best described using the accepted terminology reported by Reiss and Hahnewald (2011). Using this nomenclature, the three most commonly reported variants are c.956G>A (p.Arg319Gln), c.418+1G>A (both variants affect the MOCS1A protein) and c.1523_1524del (which affects the MOCS1B portion of the fusion protein) (Reiss and Johnson, 2003. PubMed ID: 12754701; Reiss and Hahnewald, 2011. PubMed ID: 21031595).

Biosynthesis of the molybdopterin cofactor begins with the conversion of guanosine triphosphate (GTP) to a precursor molecule designated Precursor Z. The MOCS1A and MOCS1B proteins are responsible for this step in molybdopterin biosynthesis (Arenas et al., 2009. PubMed ID: 19544009; Johnson and Duran, 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

In the largest report of biochemically confirmed molybdenum cofactor deficient patients, ~58% were found to have variants in the MOCS1 gene, ~38% in MOCS2, and 2% in GPHN (Reiss and Johnson, 2003. PubMed ID: 12754701). Analytical sensitivity should be near 100% because all reported pathogenic variants are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the MOCS1 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 molybdenum cofactor deficiency excrete elevated levels of sulfite, thiosulfate, S-sulfocysteine, xanthine, and hypoxanthine while uric acid levels are low. Family members of patients who have known MOCS1 pathogenic variants are also good candidates. We will also sequence the MOCS1 gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
MOCS1 603707
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Molybdenum Cofactor Deficiency Type A AR 252150

Citations

  • Arenas et al., 2009. PubMed ID: 19544009
  • Gray and Nicholls, 2000. PubMed ID: 10917590
  • Gümüs et al., 2010. PubMed ID: 20573177
  • Human Gene Mutation Database (Bio-base).
  • Johnson and Duran, 2014. Molybdenum Cofactor Deficiency and Isolated Sulfite Oxidase Deficiency. Online Metabolic & Molecular Bases of Inherited Disease, New York, NY: McGraw-Hill.
  • Macaya et al., 2005. PubMed ID: 16429380
  • Mendel, 2009. PubMed ID: 19623604
  • Reiss and Hahnewald, 2011. PubMed ID: 21031595
  • Reiss and Johnson, 2003. PubMed ID: 12754701
  • Reiss et al., 1998. PubMed ID: 9731530

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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