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Fanconi Anemia via the SLX4/FANCP 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
11695 SLX4 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11695SLX481479 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

  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

Fanconi anemia (FA) is considered a blood disorder; however, the clinical features of FA expand well beyond hematologic disorders alone.  FA is characterized by a range of physical abnormalities, bone marrow failure (aplastic anemia), pancytopenia, and predisposition to cancers—particularly acute myelogenous leukemia (AML), gynecologic and GI tract cancers, and cancers of the head and neck  (Auerbach. Mutat Res 668:4-10, 2009). FA patients are up to 800-fold more susceptible to AML than the general population with a median age of onset of 13 years (Rosenberg et al. Blood 101:822, 2003). Physical abnormalities include radial ray defects (absent thumb or radius), skin pigmentation defects, short stature, microphthalmia, renal and urinary tract defects, genital defects (males in particular), gastrointestinal malformations (atresia), congenital heart disease, hearing and central nervous system defects, and general developmental delay (Tischkowitz and Hodgson. J Med Genet 40:1-10, 2003; Dokal. Baillieres Best Pract Res Clin Haematol 13:407-425, 2000). About one-third of FA patients have no obvious physical abnormalities and are diagnosed only after a family member is diagnosed or after developing hematologic anomalies such as thromobocytopenia, leukopenia, and anemia (Giampietro et al. Am J Med Genet 68:58-61, 1997). A hallmark of FA is hypersensitivity of chromosomes to interstrand cross linking agents such as diepoxybutane (DEB) or mitomycin C (MMC; Sasaki and Tonomura. Cancer Res 33:1829-1836, 1973). Exposure of primary cell cultures from FA patients to DEB or MMC results in chromosomal aberrations (breaks, radials, rearrangements) due to damaged DNA repair mechanisms that require functional products of the Fanconi anemia genes. For example, the FANCA, -B, -C, -E, -F, -G, -L, and -M proteins are part of a nuclear core complex that regulates monoubiquitination of the FANCD2 and FANCI proteins (ID complex) during S-phase and after exposure to DNA crosslinking agents (Moldovan and D'Andrea. Annu Rev Genet 43:223, 2009). In unaffected individuals, ubiquitination helps localize the ID complex to sites of DNA damage and facilitate repair (Grompe, and van de Vrugt. Developmental Cell 12:661, 2007; Smogorzewska et al. Cell 129:289, 2007), but in FA patients, this mechanism is impaired.

Genetics

FA is a genetically heterogeneous autosomal recessive disorder. To date, 16 FA or FA-like genes have been discovered. Approximately 86% of all cases are attributed to variants in three genes: FANCA (~60%; OMIM 607139), FANCC (~16%; OMIM 227645), and FANCG (~10%; OMIM 602956;) (Auerbach. Mutat Res 668:4-10, 2009). Nearly 95% of all cases are attributed to variants in the eight genes (FANCA, -B, -C, -E, -F, -G, -L, and -M) that encode components of a nuclear core complex required for ID complex ubiquitination and facilitation of DNA repair (Grompe, and van de Vrugt. Developmental Cell 12:661, 2007). In the United States, the carrier frequency for FA is estimated at 1 in 181, and the incidence rate of FA is estimated at 1 in 131,000 (http://www.fanconi.org/; Rosenberg et al. Am J Med Genet A 155:1877, 2011). With the exception of FANCD1 and FANCN patients who seem to have more severe clinical symptoms, obvious genotype-phenotype correlations are lacking, and related individuals who harbor a common variant(s) may have drastically different phenotypes. Variants in SLX4 account for a small fraction of FA cases and include some missense and splicing variants but also small deletions or insertions and at least one large deletion (www.rockefeller.edu/fanconi/mutate/). No predominant variants in the SLX4 gene have been identified, and FA patients with SLX4 variants may have a milder phenotype than FA patients with variants in other FA genes (Kim et al. Nat Genet 43:142, 2011).

Clinical Sensitivity - Sequencing with CNV PGxome

Variants in known FA genes are found in >95% of cases. SLX4 variants are an infrequent cause of FA.

Testing Strategy

This test provides full coverage of all coding exons of the SLX4 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

Patients with clinical features of FA and positive chromosome breakage tests, patients with a family history of FA and/or cancer, and patients who develop aplastic anemia at any age. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLX4.

Gene

Official Gene Symbol OMIM ID
SLX4 613278
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Fanconi Anemia, Complementation Group P AR 613951

Citations

  • Auerbach AD. 2009. Fanconi anemia and its diagnosis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 668: 4–10. PubMed ID: 19622403
  • Dokal I. 2000. The genetics of Fanconi’s anaemia. Baillieres Best Pract. Res. Clin. Haematol. 13: 407–425. PubMed ID: 11030042
  • Giampietro PF, Verlander PC, Davis JG, Auerbach AD. 1997. Diagnosis of Fanconi anemia in patients without congenital malformations: an international Fanconi Anemia Registry Study. Am. J. Med. Genet. 68: 58–61. PubMed ID: 8986277
  • Grompe M, and Van de Vrugt, H. 2007. The Fanconi Family Adds a Fraternal Twin. Developmental Cell 12: 661–662. PubMed ID: 17488615
  • Kim, Y., et al., (2011). PubMed ID: 21240275
  • Moldovan G-L, D’Andrea AD. 2009. How the Fanconi Anemia Pathway Guards the Genome. Annual Review of Genetics 43: 223–249. PubMed ID: 19686080
  • Rosenberg PS, Greene MH, Alter BP. 2003. Cancer incidence in persons with Fanconi anemia. Blood 101: 822–826. PubMed ID: 12393424
  • Rosenberg PS, Tamary H, Alter BP. 2011. How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel. American Journal of Medical Genetics Part A 155: 1877–1883. PubMed ID: 21739583
  • Sasaki MS, Tonomura A. 1973. A high susceptibility of Fanconi’s anemia to chromosome breakage by DNA cross-linking agents. Cancer Research 33: 1829–1836. PubMed ID: 4352739
  • Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald ER, Hurov KE, Luo J, Ballif BA, Gygi SP, Hofmann K, D’Andrea AD, Elledge SJ. 2007. Identification of the FANCI Protein, a Monoubiquitinated FANCD2 Paralog Required for DNA Repair. Cell 129: 289–301. PubMed ID: 17412408
  • Tischkowitz MD, Hodgson SV. 2003. Fanconi anaemia. Journal of medical genetics 40: 1–10. PubMed ID: 12525534

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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