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Diamond-Blackfan Anemia and Bone Marrow Failure via the RPL11 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
8641 RPL11 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8641RPL1181479 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.

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

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. PubMed ID: 11030041; Gazda and Sieff. 2006. PubMed ID: 16942586). Physical anomalies such as craniofacial dysmorphism, thumb and neck anomalies, congenital heart defects, and genitourinary tract defects are found in ~40% of patients. Growth retardation is observed in ~30% of patients (Clinton and Gazda. 2016. PubMed ID: 20301769). Onset of hematologic complications typically occurs in the first year of life. 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. PubMed ID: 16942586), RPL5 (Gazda et al. 2008. PubMed ID: 19061985), RPL11 (Gazda et al. 2008. PubMed ID: 19061985), RPL35a (Farrar et al. 2008. PubMed ID: 18535205), RPS26 (Doherty et al. 2010. PubMed ID: 20116044), RPS24 (Gazda et al. 2006. PubMed ID: 17186470), RPS17 (Gazda et al. 2008. PubMed ID: 19061985), RPS7 (Gazda et al. 2008. PubMed ID: 19061985), RPS10 (Doherty et al. 2010. PubMed ID: 20116044), RPL26 (Gazda et al. 2012. PubMed ID: 22431104), RPS27 (Wang et al. 2015. PubMed ID: 25424902), RPS29 (Mirabello et al. 2014. PubMed ID: 24829207), RPL31 (Farrar et al. 2014. PubMed ID: 25042156), RPS28 (Gripp et al. 2014. PubMed ID: 24942156), RPL15 (Landowski et al. 2013. PubMed ID: 23812780), RPL27 (Wang et al. 2015. PubMed ID: 25424902), or by variants in the GATA1 (Sankaran et al. 2012. PubMed ID: 22706301) or TSR2 (Gripp et al. 2014. PubMed ID: 24942156) genes. Variants in the RPS19 gene are found in up to 25% of patients (Gazda and Sieff. 2006. PubMed ID: 16942586). Variants in the RPL5 (6.6%), RPS26 (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. PubMed ID: 20301769). Approximately 65% of DBA cases are found to have a pathogenic variant in one of the DBA genes (Clinton and Gazda. 2016. PubMed ID: 20301769). 55-60% of DBA cases result from de novo pathogenic variants (Clinton and Gazda. 2016. PubMed ID: 20301769) 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.

Variants in the RPL11 gene are reported in 4.8% of DBA patients (Clinton and Gazda. 2016. PubMed ID: 20301769). Small insertions or deletions of only a few nucleotides resulting in frameshifts, and variants that affect splicing, are the most frequent variant types reported to cause RPL11-associated DBA. Missense variants in RPL11 are an infrequent cause of disease.

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 - Sequencing with CNV PGxome

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. PubMed ID: 20301769). Variants in the RPS19 gene are found in up to 25% of patients (Gazda and Sieff. 2006. PubMed ID: 16942586). Variants in the RPL5 (6.6%), RPS26 (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. PubMed ID: 20301769).

Testing Strategy

This test provides full coverage of all coding exons of the RPL11 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 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 potential donors and 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.

Gene

Official Gene Symbol OMIM ID
RPL11 604175
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Diamond-Blackfan Anemia 7 AD 612562

Related Tests

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

Citations

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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