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Diamond-Blackfan Anemia and Bone Marrow Failure via the RPS17 Gene

Summary and Pricing

Test Method

Bi-Directional Sanger Sequencing
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
2759 RPS17 81479 81479 $540 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
2759RPS1781479 81479 $540 Order Options and Pricing

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

Turnaround Time

4 weeks on average for standard orders or 2 weeks 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

Diamond-Blackfan anemia (DBA) is a rare, inherited bone marrow failure syndrome characterized by macrocytic anemia, normal leukocyte and platelet numbers, and normocellular bone marrow (Freedman 2000; Gazda and Sieff 2006). Physical anomalies such as craniofacial dysmorphism, thumb and neck anomalies, congenital heart defects, and genitourinary tract defects are found in ~40% of patients and growth retardation is observed in ~30% of patients (Clinton and Gazda 2016). Onset of hematologic complications typically occurs in the first year of life, and the severity of disease varies from mild anemia with no physical anomalies to severe anemia and severe physical anomalies. DBA is also associated with bone marrow failure and increased risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Genetics

DBA is an autosomal dominant or X-linked disorder caused by inactivating variants within ribosomal protein genes RPS19 (Gazda and Sieff 2006), RPL5 (Gazda et al. 2008), RPL11 (Gazda et al. 2008), RPL35a (Farrar et al. 2008), RPS26 (Doherty et al. 2010), RPS24 (Gazda et al. 2006), RPS17 (Gazda et al. 2008), RPS7 (Gazda et al. 2008), RPS10 (Doherty et al. 2010), RPL26 (Gazda et al. 2012), RPS27 (Wang et al. 2015), RPS29 (Mirabello et al. 2014), RPL31 (Farrar et al. 2014), RPS28 (Gripp et al. 2014), RPL15 (Landowski et al. 2013), RPL27 (Wang et al. 2015), or by variants in the GATA1 (Sankaran et al. 2012) or TSR2 (Gripp et al. 2014) genes. Variants in the RPS19 gene are found in up to 25% of patients (Gazda and Sieff 2006). Variants in the RPL5 (6.6%), PRS26 (6.4%), RPL11 (4.8%), RPL35A (3%), RPS10 (2.6%), RPS24 (2%), and RPS17 (1%) genes are the next most frequent causes of DBA with variants in all other associated genes accounting for a very small fraction of disease (Clinton and Gazda 2016). Approximately 65% of DBA cases are found to have a pathogenic variant in one of the DBA genes (Clinton and Gazda 2016), and 55-60% of DBA cases result from de novo pathogenic variants (Clinton and Gazda 2016) with the remainder of cases resulting from inheritance of a pathogenic variant from an affected parent.

DBA results from loss of protein function and haploinsufficiency. Pathogenic variants consist primarily of missense variants and nonsense or other protein truncating variants including frameshift deletions and insertions. Large, multi-exon or full gene deletions of several ribosomal proteins, in particular RPS19, RPL5, RPL11, RPL35A, RPS26, RPS24, RPS17, and RPL15, have been reported in patients with DBA. Dysfunctional ribosomal proteins are likely to alter the stability and/or function of the ribosomal complex causing destruction of blood-forming cells in the bone marrow and consequent anemia.

Other bone marrow failure syndromes such as Fanconi anemia, severe congenital neutropenia, dyskeratosis congenital, and Shwachman-Diamond syndrome should be considered in addition to DBA during diagnosis.

Clinical Sensitivity - Sanger Sequencing

Approximately 65% of Diamond-Blackfan anemia (DBA) cases are found to have a pathogenic variant in one of the DBA genes (Clinton and Gazda 2016). Variants in the RPS19 gene are found in up to 25% of patients (Gazda and Sieff 2006). Variants in the RPL5 (6.6%), PRS26 (6.4%), RPL11 (4.8%), RPL35A (3%), RPS10 (2.6%), RPS24 (2%), and RPS17 (1%) genes are the next most frequent causes of DBA, with variants in all other associated genes accounting for a very small fraction of disease (Clinton and Gazda 2016).

Testing Strategy

Our DNA sequencing test involves bidirectional DNA sequencing of all coding exons (exons 1-5) of the RPS17 gene plus ~10 bp of flanking non-coding DNA on either side of each exon. We will also sequence any single exon (Test #100) in family members of patients with a known pathogenic variant or to confirm research results.

Indications for Test

Patients with symptoms of Diamond - Blackfan anemia or indication of bone marrow failure or MDS/AML are candidates for this test. Other candidates for this test include patients with an indication of bone marrow failure and who have tested negative for other bone marrow failure disorders such as Fanconi anemia, Shwachman - Diamond syndrome, dyskeratoris congenita, and severe congenital neutropenia, and potential bone marrow donors.

Gene

Official Gene Symbol OMIM ID
RPS17 180472
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Diamond-Blackfan Anemia 4 AD 612527

Citations

  • Clinton C. and Gazda H.T. 2016. Diamond-Blackfan Anemia. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301769
  • Doherty L. et al. 2010. American Journal of Human Genetics. 86: 222-8. PubMed ID: 20116044
  • Farrar J.E. et al. 2008. Blood. 112: 1582-92. PubMed ID: 18535205
  • Farrar J.E. et al. 2014. American Journal of Hematology. 89: 985-91. PubMed ID: 25042156
  • Freedman M.H. 2000. Bailleres Best Practice and Research Clinical Haematology. 13: 391-406. PubMed ID: 11030041
  • Gazda H.T. et al. 2006. American Journal of Human Genetics. 79: 1110-8. PubMed ID: 17186470
  • Gazda H.T. et al. 2008. American Journal of Human Genetics. 83: 769-80. PubMed ID: 19061985
  • Gazda H.T. et al. 2012. Human Mutation. 33: 1037-44. PubMed ID: 22431104
  • Gazda H.T., Sieff C.A. 2006. British Journal of Haematology. 135: 149-57. PubMed ID: 16942586
  • Gripp K.W. et al. 2014. American Journal of Medical Genetics. Part A. 164A: 2240-9. PubMed ID: 24942156
  • Landowski M. et al. 2013. Human Genetics. 132: 1265-74. PubMed ID: 23812780
  • Mirabello L. et al. 2014. Blood. 124: 24-32. PubMed ID: 24829207
  • Sankaran V.G. et al. 2012. The Journal of Clinical Investigation. 122: 2439-43. PubMed ID: 22706301
  • Wang R. et al. 2015. British Journal of Haematology. 168: 854-64. PubMed ID: 25424902

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

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ORDER OPTIONS

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View Ordering Instructions

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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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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