Diamond-Blackfan Anemia Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
3015 RPL11 81479,81479 Order Options and Pricing
RPL15 81479,81479
RPL26 81479,81479
RPL35A 81479,81479
RPL5 81479,81479
RPS10 81479,81479
RPS17 81479,81479
RPS19 81405,81479
RPS24 81479,81479
RPS26 81479,81479
RPS7 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
3015Genes x (11)81479 81405, 81479 $1030 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

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. Pathogenic 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 protein genes, 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 congenita, 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). Pathogenic 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). We note that missense, nonsense, and splicing variants are the most frequent types of pathogenic variants found in most DBA-related genes. Large deletions have also been reported in most DBA-related genes, in particular, large deletions in the RPS17, RPS19, and RPS26 genes are a frequent cause of disease. For the RPL15 gene, one large deletion of the whole gene and one deletion of exon 4 are the only pathogenic variants reported for the gene.

Testing Strategy

Due to high paralogy between the RPS17 gene and other regions of the genome, CNV analysis of the RPS17 gene is NOT included in this test.

This panel provides full 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.

Due to high paralogy between the RPS17 gene and other regions of the genome, Sanger sequencing, using custom-designed primers, will be used to cover all coding exons (exons 1-5) of the RPS17 gene plus ~10 bp of flanking non-coding DNA on either side of each exon.

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

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, dyskeratosis congenita, and severe congenital neutropenia.

Genes

Official Gene Symbol OMIM ID
RPL11 604175
RPL15 604174
RPL26 603704
RPL35A 180468
RPL5 603634
RPS10 603632
RPS17 180472
RPS19 603474
RPS24 602412
RPS26 603701
RPS7 603658
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

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.

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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