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Alport Syndrome via the COL4A4 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
11193 COL4A4 81407 81407,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11193COL4A481407 81407(x1), 81479(x1) $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

Alport Syndrome (AS) is a hereditary nephritis caused by defects of the collagen type IV protein, which is responsible for basement membrane formation in the kidney, ear and eye. The disease affects approximately 1 in 50000 individuals and is characterized by progressive renal failure, sensorineural hearing loss and eye abnormalities. The most common symptoms include persistent microhematuria at early childhood, progressive proteinuria, bilateral high frequency sensorineural hearing loss and anterior lenticonus in late childhood and adolescence. Approximately 85% of cases are X-linked caused by COL4A5 gene, and the remaining cases are inherited in autosomal recessive (15%) and autosomal dominant manner (5%). Mutations in the COL4A4 gene cause autosomal recessive and dominant Alport syndrome. COL4A4 gene mutations also cause Benign Familial Hematuria (also called Thin-Basement Membrane Nephropathy) (van der Loop et al. 2000; Mochizuki et al. 1994; Nagel et al. 2005; Hertz. 2009; Kashtan 2010).

Genetics

Alport syndrome can be caused by mutations in COL4A3, COL4A4 and COL4A5. The COL4A4  gene encodes alpha-4 chain of type IV collagen, a major structural component of basement membranes. To date, more than 70 causative mutations were reported throughout the COL4A4 gene. 60% of mutations are truncating mutations in AR cases (Hertz 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

COL4A3 and COL4A4 mutations account for approximately 20% of Alport syndrome cases (Kashtan 2013). To date, 57% of clinical suspected autosomal recessive Alport patients have mutations in COL4A3 or COL4A4 genes (Zhang et al. 2012). The COL4A3 or COL4A4 mutation detection rate should be higher in families fulfilling three or more clinical diagnostic criteria (Hertz et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the COL4A4 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 symptoms consistent with autosomal dominant, autosomal recessive Alport syndrome, and the family members of patients who have known COL4A4 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in COL4A4.

Gene

Official Gene Symbol OMIM ID
COL4A4 120131
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Alport Syndrome, Autosomal Recessive AR 203780

Citations

  • Hertz JM, Thomassen M, Storey H, Flinter F. 2012. Clinical utility gene card for: Alport syndrome. European Journal of Human Genetics 20:doi: 10.1038. PubMed ID: 22166944
  • Hertz JM. 2009. Alport syndrome. Molecular genetic aspects. Dan Med Bull 56: 105–152. PubMed ID: 19728970
  • Kashtan CE. 2013. Alport Syndrome and Thin Basement Membrane Nephropathy. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301386
  • Mochizuki T, Lemmink HH, Mariyama M, Antignac C, Gubler MC, Pirson Y, Verellen-Dumoulin C, Chan B, Schröder CH, Smeets HJ. 1994. Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. Nat. Genet. 8: 77-81. PubMed ID: 7987396
  • Nagel et al. Novel COL4A5, COL4A4, and COL4A3 mutations in Alport syndrome. Hum Mutat  26(1): 60. 2005. PubMed ID: 15954103
  • Van Der Loop FT, Heidet L, Timmer ED, Den Bosch BJ Van, Leinonen A, Antignac C, Jefferson JA, Maxwell AP, Monnens LA, Schröder CH, others. 2000. Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation. Kidney international 58: 1870–1875. PubMed ID: 11044206
  • Zhang Y, Wang F, Ding J, Zhang H, Zhao D, Yu L, Xiao H, Yao Y, Zhong X, Wang S. 2012. Genotype-phenotype correlations in 17 Chinese patients with autosomal recessive Alport syndrome. American Journal of Medical Genetics Part A 158A: 2188-2193. PubMed ID: 22887978

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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