Gaucher Disease via the GBA Gene

Summary and Pricing

Test Method

Bi-Directional Sanger Sequencing
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT Prenatal
479 GBA$990 8147981479 Add to Order

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

14 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

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).

Genetics

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.

Clinical Sensitivity - Sanger Sequencing

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). 

Indications for Test

Patients with clinical diagnosis of Gaucher disease and heterozygous carrier relatives are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GBA.

Gene

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

Citations

  • 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
  • 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
  • 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. 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

Ordering/Specimens

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.

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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