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Thiamine Responsive Megaloblastic Anemia via the SLC19A2 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
9997 SLC19A2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9997SLC19A281479 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

  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

Thiamine Responsive Megaloblastic Anemia (TRMA), also known as Roger’s syndrome, is characterized by a phenotypic triad of megaloblastic anemia, non-type I diabetes mellitus, and sensorineural deafness. To date, less than 100 cases have been described worldwide. TRMA onset occurs between infancy and adolescence, however all key features are not initially present (Bergmann et al. 2009). Megaloblastic anemia results in loss of appetite, headache, pallor, lethargy, and paresthesia in hands and feet. In some cases retinal dystrophy, optic nerve atrophy, short stature, congenital heart defects, seizures, and strokes have been reported. Treatment of TRMA includes daily thiamine to alleviate anemia; however, thiamine is unable to improve sensorineural deafness. Genetic testing is helpful in the differential diagnosis of TRMA from Wolfram syndrome, mitochondrial disorders, acquired forms of megaloblastic anemia, myelodysplastic syndromes, and juvenile forms of diabetes (Oishi et al. 1993).

Genetics

TRMA is inherited in an autosomal recessive manner through pathogenic variants in the SLC19A2 gene. SLC19A2 encodes a thiamine transporter and is the sole transporter in bone marrow, pancreatic beta cells, and a subset of cochlear cells (Diaz et al. 1999; Fleming et al. 1999). Truncating variants are most common with nonsense, frameshift, and splice site alterations accounting for the majority of TRMA cases (Bergmann et al. 2009; Raz et al. 2000). Missense variants have also been reported in TRMA patients and are predicted to result in impair protein function or intracellular trafficking (Bergmann et al. 2009). Gross deletions have only been reported in one case (Oishi et al. 1993) There is no clear genotype-phenotype presentation, but TRMA is fully penetrant (Oishi et al. 1993). Pathogenic variants are largely private and have been reported throughout the entire SLC19A2 gene (Bergmann et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated due to the limited number of patients being reported. To date, the SLC19A2 gene is the only known cause of TRMA. Analytical sensitivity is estimated at >95% as gross deletions have only been reported in one case (Oishi et al. 1993).

Testing Strategy

This test provides full coverage of all coding exons of the SLC19A2 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

Candidates for testing present with phenotypic triad of megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. Bone marrow biopsies typically have a combination of megaloblasts and ringed sideroblasts (Oishi et al. 1993). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC19A2.

Gene

Official Gene Symbol OMIM ID
SLC19A2 603941
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Thiamine Responsive Megaloblastic Anemia Syndrome AR 249270

Citations

  • Bergmann A.K. et al. 2009. The Journal of Pediatrics. 155: 888-892.e1. PubMed ID: 19643445
  • Diaz G.A. et al. 1999. Nature Genetics. 22: 309-12. PubMed ID: 10391223
  • Fleming J.C. et al. 1999. Nature Genetics. 22: 305-8. PubMed ID: 10391222
  • Oishi K. et al. 1993. PubMed ID: 20301459
  • Raz T. et al. 2000. Human Mutation. 16: 37-42. PubMed ID: 10874303

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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