Alport Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10147 COL4A3 81408,81479 Order Options and Pricing
COL4A4 81407,81479
COL4A5 81408,81407
COL4A6 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10147Genes x (4)81479 81407, 81408, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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

For Reflex to PGxome pricing click here.

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 in collagen type IV protein, which is responsible for basement membrane formation in the kidney, ear and eye. The disease affects approximately 1 in 50,000 individuals and is characterized by progressive renal failure, sensorineural hearing loss and eye abnormalities. The most common symptoms include persistent microhematuria in early childhood, progressive proteinuria, bilateral high frequency sensorineural hearing loss and anterior lenticonus in late childhood and adolescence (Kashtan 2013).

Genetics

Approximately 80% of Alport syndrome cases are X-linked caused by mutations in the COL4A5 gene; the remaining cases are inherited in an autosomal recessive (15%) and autosomal dominant manner (5%) caused by mutations in either in COL4A3 or COL4A4. Heterozygous mutations in COL4A3 and COL4A4 can 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 et al. 2009). Large deletions involving 5’ ends of the COL4A5 gene and a breakpoint within intron 2 of the COL4A6 gene were reported to cause diffuse leiomyomatosis (Uliana et al. 2011). A missense mutation in the COL4A6 gene was reported to cause X-linked non-syndromic hearing loss in one Hungarian family (Rost et al. 2014). Some heterozygous female carriers of the COL4A5 pathogenic mutations may develop some clinical features, and their clinical manifestations are variable largely determined by random X-inactivation. ~95% of female carriers have hematuria (Jais et al. 2003).

To date, more than 600 unique causative COL4A5 mutations have been reported throughout the gene including missense (~42%, more than 85% of these missense mutations affect a glycine residue), nonsense (6%), splicing (17%), small deletion/insertion (22%), and large deletion/insertion (~13%) and complex large rearrangements (1%) (King et al. 2006; Human Gene Mutation Database). Almost 140 pathogenic COL4A3 mutations have been reported. They are: missense (~44%, more than 70% of these missense mutations affect a glycine residue), nonsense (12%), splicing (15%), small deletion/insertion (28%), and only two large deletions, respectively (Oka et al. 2014; Human Gene Mutation Database). More than 90 pathogenic COL4A4 mutations have been reported throughout the gene. They are: missense (~54%, more than 70% of these missense mutations affect a glycine residue), nonsense (8%), splicing (10%), small deletion/insertion (25%), and only one large deletion (Oka et al. 2014; Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

A large panel study showed that the overall detection rate is 53%, and a likely causative mutation was identified in 82% (23/28) of families with clear X-linked cases (Hertz 2009). Approximately 57% of clinical suspected autosomal recessive Alport syndrome patients have mutations in COL4A3 or COL4A4 (Zhang et al. 2012).

Large deletions/duplications and complex large rearrangements account for ~15% of pathogenic mutations found in COL4A5 (King et al. 2006; Human Gene Mutation Database). However, only a few large deletions involving COL4A3 and COL4A4 have been identified (Oka et al. 2014; Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with symptoms consistent with clinical diagnosed Alport syndrome, benign familial hematuria and the family members of patients who have known mutations in COL4A5, COL4A4, COL4A3 and COL4A6.

Genes

Official Gene Symbol OMIM ID
COL4A3 120070
COL4A4 120131
COL4A5 303630
COL4A6 303631
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Hertz JM. 2009. Alport syndrome. Molecular genetic aspects. Dan Med Bull 56: 105–152. PubMed ID: 19728970
  • Human Gene Mutation Database (Bio-base).
  • Jais JP. 2003. X-Linked Alport Syndrome: Natural History and Genotype-Phenotype Correlations in Girls and Women Belonging to 195 Families: A “European Community Alport Syndrome Concerted Action” Study. Journal of the American Society of Nephrology 14: 2603-2610. PubMed ID: 14514738
  • 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
  • King K, Flinter FA, Green PM. 2006. A two-tier approach to mutation detection in the COL4A5 gene for Alport syndrome. Human Mutation 27: 1061–1061. PubMed ID: 16941480
  • 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
  • Oka M, Nozu K, Kaito H, Fu XJ, Nakanishi K, Hashimura Y, Morisada N, Yan K, Matsuo M, Yoshikawa N, Vorechovsky I, Iijima K. 2014. Natural history of genetically proven autosomal recessive Alport syndrome. Pediatric Nephrology. PubMed ID: 24633401
  • Rost S, Bach E, Neuner C, Nanda I, Dysek S, Bittner RE, Keller A, Bartsch O, Mlynski R, Haaf T, Müller CR, Kunstmann E. 2014. Novel form of X-linked nonsyndromic hearing loss with cochlear malformation caused by a mutation in the type IV collagen gene COL4A6. Eur. J. Hum. Genet. 22: 208-215. PubMed ID: 23714752
  • Uliana V, Marcocci E, Mucciolo M, Meloni I, Izzi C, Manno C, Bruttini M, Mari F, Scolari F, Renieri A, Salviati L. 2011. Alport syndrome and leiomyomatosis: the first deletion extending beyond COL4A6 intron 2. Pediatric Nephrology 26: 717-724. PubMed ID: 21380622
  • 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

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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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