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

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
2759 RPS17$540.00 81479 Add to Order
Targeted Testing

For ordering sequencing of targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

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).

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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).


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.

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.


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


Name Inheritance OMIM ID
Diamond-Blackfan Anemia 4 AD 612527

Related Test

Autism Spectrum Disorders and Intellectual Disability (ASD-ID) Comprehensive Sequencing Panel with CNV Detection


Genetic Counselors
  • 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
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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