Alport Syndrome via the COL4A3 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
3121 COL4A3 81408 81408,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3121COL4A381408 81408, 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

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 during early childhood and progressive proteinuria, bilateral high frequency sensorineural hearing loss and anterior lenticonus in late childhood and adolescence. Approximately 80% of cases are X-linked; the remaining cases are inherited in an autosomal recessive (15%) and autosomal dominant manner (5%). Mutations in the COL4A3 gene cause autosomal recessive and dominant Alport syndrome. COL4A3 gene mutations also cause Benign Familial Hematuria (also called Thin-Basement Membrane Nephropathy) (Lemmink et al. 1994; van der Loop et al. 2000; Nagel et al. 2005; Hertz 2009; Kashtan 2013).

Genetics

Alport syndrome can be caused by mutations in COL4A3, COL4A4 and COL4A5. The COL4A3 gene encodes the alpha-3 chain of type IV collagen, a major structural component of basement membranes. To date, more than 70 causative mutations were reported throughout the gene. 60% of causative mutations are truncating in AR cases (Hertz. 2009).

Clinical Sensitivity - Sequencing with CNV PG-Select

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 the 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 COL4A3 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with symptoms consistent with autosomal dominant, autosomal recessive Alport syndrome, patients affected with thin-basement membrane nephropathy, and the family members of patients who have known COL4A3 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in COL4A3.

Gene

Official Gene Symbol OMIM ID
COL4A3 120070
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

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
  • Lemmink et al.  Mutations in the type IV collagen alpha 3 (COL4A3) gene in autosomal recessive Alport syndrome. Hum Molec Genet 3(8):1269-1273, 1994. PubMed ID: 7987301
  • 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.

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

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ORDER OPTIONS

View Ordering Instructions

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.

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