Bernard-Soulier Syndrome Sanger Sequencing Panel

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits


Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
432 GP1BA$580.00 81479 Add to Order
GP1BB$490.00 81404
GP9$370.00 81479
Full Panel Price* $1220.00
Pricing Comment

When two or more genes in the panel are tested, the price will be 85% of the sum of the individual gene prices.

Targeted Testing

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

Turnaround Time

The great majority of Sanger panels are completed within 2-4 weeks.

Clinical Sensitivity

85% of patients harbored homozygous variants in one of the three known causative genes while 13% of patients were compound heterozygous (Savoia et al. 2014). Causative variants have been identified to date in GP1BA (28%), GP1BB (28%), and GP9 (44%), but not in GP5 (Savoia et al. 2014).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 GP1BA$690.00 81479 Add to Order
GP1BB$690.00 81479
GP9$690.00 81479
Full Panel Price* $770.00
Pricing Comment

# of Genes Ordered

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Over 100

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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Though several small deletions have been reported in the GP1BA and GP9 genes, to our knowledge, large multi-exon or full-gene deletions involving the GP1BA and GP9 genes have not been reported in patients with Bernard-Soulier syndrome. Large deletions in the GP1BB gene have been reported in patients with BSS, though they are rare causes of BSS. In particular, a large deletion of 22q11.2 involving the entire GP1BB gene has been reported in patients with BSS and in patients with DiGeorge syndrome. Our gene-cantric aCGH test will detect multi-exon and full gene deletions of the GP1BB gene. If testing for the larger 22q11.2 deletion is desired, we recommend our chromosomal microarray (CMA) test (test number 2000).

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Clinical Features

Bernard-Soulier Syndrome (BSS) (also sometimes called Giant Platelet Syndrome) is a bleeding disorder characterized mainly by mild-moderate thrombocytopenia with large platelets, spontaneous muco-cutaneous bleeding, and post-traumatic bleeding. Onset is typically in infancy or childhood, but patients may not receive a diagnosis until later in life and/or may be misdiagnosed with immune thrombocytopenia (Kunishima et al. 2006; Balduini et al. 2013; Moiz and Rashid 2013). The incidence of BSS is estimated at 1 per 1 million live births (Savoia et al. 2014; Savoia et al. 2011).


Bernard-Soulier Syndrome is primarily an autosomal recessive disorder, although variants that display autosomal dominant inheritance have been reported for the GP1BA and GP1BB genes (Savoia et al. 2001; Noris et al. 2012; Kunishima et al. 2001). A detailed study of BSS patients revealed that 85% of patients harbored homozygous variants in one of the three known causative genes while 13% of patients were compound heterozygous (Savoia et al. 2014). Causative variants have been identified to date in GP1BA (28%), GP1BB (28%), and GP9 (44%), but not in GP5 (Savoia et al. 2014). Missense and nonsense variants predominate in cases of BSS, though small and large deletions, and variants in regulatory regions have also been reported (Lanza 2006). A microdeletion on chromosome 22q11.2 that includes GP1BB has been identified in patients with BSS and in patients with DiGeorge syndrome who have cardiac and dysmophic facial features in addition to macrothrombocytopenia and bleeding diathesis (Budarf et al. 1995; McDonald-McGinn et al. 2015). One dominant variant in GP1BA defined as p.Ala172Val (aka p.Ala156Val, the Bolzano mutation) is common among Italians (Savoia et al. 2001, Noris et al. 2012) and several variants in GP1BB have been reported in patients with dominant macrothrombocytopenia (Kunishima et al. 2001; Sivapalaratnam et al. 2017). Gain of function variants in GP1BA have also been reported to cause dominant Pseudo-von Willebrand Disease (VWPD) that is characterized by thrombocytopenia resulting from increased platelet aggregation and consequent removal from circulation (Savoia et al. 2014).

BSS is caused by defects in the platelet membrane receptor complex (aka GPIB-IX-V complex) that binds von Willebrand factor at sites of vascular injury during platelet activation and thrombus formation (López et al. 1998). The GPIB-IX-V complex comprises four glycoprotein (GP) subunits: GPIbα, GPIbβ, GPIX and GPV encoded respectively by the GP1BA, GP1BB, GP9 and GP5 genes (López et al. 1998). Platelets from BSS patients generally have low levels of the GPIB-IX-V complex which fails to assemble and localize to the plasma membrane regardless of which of the subunits is perturbed by a pathogenic variant (Li and Emsley 2013).

Testing Strategy

Testing of the BSS genes will be performed sequentially in the order requested by the institution (typically GP1BA, GP1BB, then GP9). Testing involves bidirectional DNA sequencing of the full coding regions of the BSS genes along with ~20 bp of flanking DNA on either side of each exon. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.

Indications for Test

All patients with symptoms of BSS and macrothrombocytopenia, patients with suspected immune thrombocytopenia, and family members of patients are candidates for this test. In cases where DNA from an affected child is unavailable, we will sequence the genes in parents or other family members. 


Official Gene Symbol OMIM ID
GP1BA 606672
GP1BB 138720
GP9 173515
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

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Bernard-Soulier Syndrome via the GP1BA Gene
Bernard-Soulier Syndrome via the GP1BB Gene
Bernard-Soulier Syndrome via the GP9 Gene
Bleeding Disorders Sequencing Panel
Platelet Function Disorder Sequencing Panel
Thrombocytopenia Sequencing Panel
Thrombocytopenia Sequencing Panel - Expanded


Genetic Counselors
  • Balduini C.L. et al. 2013. Journal of Thrombosis and Haemostasis. 11: 1006-19. PubMed ID: 23510089
  • Budarf M.L. et al. 1995. Human Molecular Genetics. 4: 763-6. PubMed ID: 7633430
  • Kunishima S. et al. 2001. American Journal of Hematology. 68: 249-55. PubMed ID: 11754414
  • Kunishima S. et al. 2006. European Journal of Haematology. 76: 348-55. PubMed ID: 16519708
  • Lanza F. 2006. Orphanet Journal of Rare Diseases. 1: 46. PubMed ID: 17109744
  • López J.A. et al. 1998. Blood. 91: 4397-418. PubMed ID: 9616133
  • Li R., Emsley J. 2013. Journal of Thrombosis and Haemostasis. 11: 605-14. PubMed ID: 23336709
  • McDonald-McGinn D.M. et al. 2015. Nature Reviews. Disease Primers. 1: 15071. PubMed ID: 27189754
  • Moiz B., Rashid A. 2013. Blood. 122: 1693. PubMed ID: 24137817
  • Noris P. et al. 2012. Haematologica. 97: 82-8. PubMed ID: 21933849
  • Savoia A. et al. 2001. Blood. 97: 1330-5. PubMed ID: 11222377
  • Savoia A. et al. 2011. Haematologica. 96: 417-23. PubMed ID: 21173099
  • Savoia A. et al. 2014. Human Mutation. 35: 1033-45. PubMed ID: 24934643
  • Sivapalaratnam S. et al. 2017. Blood. 129: 520-4. PubMed ID: 28064200
Order Kits

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 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 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 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

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 20 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.

Deletion/Duplication Testing Via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

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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