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Distal Renal Tubular Acidosis, Autosomal Recessive, via the ATP6V0A4 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
11099 ATP6V0A4 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11099ATP6V0A481479 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. 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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Hereditary forms of distal renal tubular acidosis (dRTA) result from impaired acid excretion at intercalated cells in the collecting tubules and are characterized by hyperchloremic metabolic acidosis without bicarbonaturia or diarrhea (Alper 2010; Batlle et al. 2012). Common clinical features include retarded growth, osteomalacia, hypercalciuria, hypocitraturia, nephrocalcinosis, polyuria and hypokalemia. To date, known genetic defects for dRTA have found in genes encoding acid–base transporters including the basolateral anion exchanger 1 (AE1), the cytosolic carbonic anhydrase II (CA2), the B1-subunit (ATP6V1B1) and the A4 unite (ATP6V0A4) of the vacuolar H+-ATPase (V-ATPase). Hearing loss presents in approximately one-third of patients due to defects in subunits of the V-ATPase.

ATP6V0A4 pathogenic variants cause recessive dRTA with normal hearing or late onset hearing loss (Karet et al. 1999; Stover et al. 2002). This type of dRTA presents at early childhood. Of note, hearing loss has been found in the second and third decade of patients’ lives (Stover et al. 2002). Hyperammonemia has been also reported as part of the presentation (Alper 2010).

Genetics

Distal renal tubular acidosis (dRTA) with normal hearing or late onset hearing loss is an autosomal recessive disorder caused by ATP6V0A4 pathogenic variants (Karet et al. 1999; Stover et al. 2002). The ATP6V0A4 gene has 22 coding exons that encode the A4-subunit of the vacuolar H+-ATPase (V-ATPase), which regulates distal nephron acid secretion and also maintains the proper pH of the fluid in the inner ear.

Genetic defects of ATP6V0A4 found to date include missense, nonsense, splicing mutations and small deletion/insertions (Human Gene Mutation Database). Exon-level large deletions involving ATP6V0A4 have been also reported.

Clinical Sensitivity - Sequencing with CNV PGxome

In the original study that identified ATP6V0A4 pathogenic variants in autosomal recessive dRTA with normal hearing, Karet et al. studied 13 unrelated kindreds (12 had family history of consanguineous marriage) and found ATP6V0A4 pathogenic variants in 9 (68%) cases (Karet et al. 1999). In another study of 26 patients with autosomal recessive dRTA, of which 23 were consanguineous, ATP6V0A4 pathogenic variants were found in 12 (46%) cases (Stover et al. 2002).

Testing Strategy

This test provides full coverage of all coding exons of the ATP6V0A4 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 this test are patients with autosomal recessive dRTA with normal hearing or late onset hearing loss. Testing is also indicated for family members of patients who have known mutations in the ATP6V0A4 gene. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ATP6V0A4.

Gene

Official Gene Symbol OMIM ID
ATP6V0A4 605239
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Alper SL. 2010. Familial renal tubular acidosis. J. Nephrol. 23 Suppl 16: S57–76. PubMed ID: 21170890
  • Batlle D, Haque SK. 2012. Genetic causes and mechanisms of distal renal tubular acidosis. Nephrol. Dial. Transplant. 27: 3691–3704. PubMed ID: 23114896
  • Human Gene Mutation Database (Bio-base).
  • Karet FE, Finberg KE, Nayir A, Bakkaloglu A, Ozen S, Hulton SA, Sanjad SA, Al-Sabban EA, Medina JF, Lifton RP. 1999. Localization of a gene for autosomal recessive distal renal tubular acidosis with normal hearing (rdRTA2) to 7q33-34. Am. J. Hum. Genet. 65: 1656–1665. PubMed ID: 10577919
  • Stover EH, Borthwick KJ, Bavalia C, Eady N, Fritz DM, Rungroj N, Giersch ABS, Morton CC, Axon PR, Akil I, Al-Sabban EA, Baguley DM, Bianca S, Bakkaloglu A, Bircan Z, Chauveau D, Clermont MJ, Guala A, Hulton SA, Kroes H, Li Volti G, Mir S, Mocan H, Nayir A, Ozen S, Rodriguez Soriano J, Sanjad SA, Tasic V, Taylor CM, Topaloglu R, Smith AN, Karet FE. 2002. Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss. J. Med. Genet. 39: 796–803. PubMed ID: 12414817

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.
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