Gaucher Disease via the GBA 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
479 GBA$850 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
This test detects GBA causative variants in ~ 99% of patients with a clinical diagnosis of Gaucher Disease Types I, II and III (Pastores and Hughes 2015). 

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Clinical Features
Gaucher Disease (GD) is one of several disorders of sphingolipid degradation, known as sphingolipidoses. Each sphingolipidosis is associated with defects of a specific lysosomal enzyme or other protein involved in sphingolipid degradation with subsequent accumulation of substrate in one or more organs. In patients with GD, a defective acid beta-glucocerebrosidase enzyme results in the progressive accumulation of glucocerebroside in reticuloendothelial cells with subsequent damage to various organs, including the liver, spleen, bone marrow, lungs and central nervous system (Brady et al. 1965). Three GD Types (I, II and III) can be distinguished, according to the presence or absence of central nervous system abnormalities, age of onset, severity and progression. The earliest manifestations of GD are usually hematological abnormalities due to hypersplenism. Additional features are variable and include cytopenia, splenomegaly and bone fractures. GD patients are also classified using the Zimran Severity Score Index (Zimran et al. 1992). GD occurs in diverse ethnic groups, with an estimate incidence of 1 in 20,000 worldwide. However, GD Type 1 is more prevalent in the Ashkenazi Jewish population, with an estimated prevalence of 1:855 and a carrier frequency of 1:18 (Beutler et al. 1993; Pastores and Hughes 2015).
Types I, II and III GD are inherited in an autosomal recessive manner and are caused by defects in the GBA gene (Tsuji et al. 1987). About 380 pathogenic variants, distributed along the entire coding region of the gene, have been reported. The majority are missense, although all types of variants have been reported, including complex rearrangements that result from homologous recombination between the functional GBA gene and its pseudogene (Tayebi et al. 2003; Human Gene Mutation Database).

At least 20 different complex alleles are known, which include recombinant alleles, fusion alleles, and gene conversions. Specifically, a 55-bp deletion that results from a gene conversion from the pseudogene is reported in up to 4% of patients (Beutler et al. 1993; Tayebi et al. 1996). This deletion occurs also as a part of a recombinant allele that includes four variants D409H, L444P, A456P and V460V (Hatton et al. 1997; Tayebi et al. 1998).

The GBA gene encodes the beta-glucocerebrosidase enzyme, which catalyzes the hydrolysis of glucocerebroside to ceramide and glucose.
Testing Strategy

This test involves bidirectional Sanger sequencing of all coding exons and splice sites of the GBA gene. The full coding sequence of each exon plus ~10 bp of flanking DNA on either side are sequenced. 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
Patients with clinical diagnosis of Gaucher disease and heterozygous carrier relatives are candidates.


Official Gene Symbol OMIM ID
GBA 606463
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Genetic Counselors
  • Beutler E. et al. 1993. American Journal of Human Genetics. 52: 85-8. PubMed ID: 8434610
  • Beutler E. et al. 1993. Genomics. 15: 203-5. PubMed ID: 8432537
  • Brady R.O. et al. 1965. Biochemical and Biophysical Research Communications. 18: 221-5. PubMed ID: 14282020
  • Hatton C.E. et al. 1997. Archives of Disease in Childhood. 77: 17-22. PubMed ID: 9279145
  • Human Gene Mutation Database (Bio-base).
  • Pastores G.M., Hughes D.A. 2015. Gaucher Disease. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301446
  • Tayebi N. et al. 1996. American Journal of Medical Genetics. 66: 316–9. PubMed ID: 8985494
  • Tayebi N. et al. 1998. Pediatric Research. 43: 571-8. PubMed ID: 9585001
  • Tayebi N. et al. 2003. American Journal of Human Genetics. 72: 519-34. PubMed ID: 12587096
  • Tsuji S. et al. 1987. The New England Journal of Medicine. 316: 570-5. PubMed ID: 2880291
  • Zimran A. et al. 1992. Medicine. 71: 337-53. PubMed ID: 1435229
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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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