Gaucher Disease (GBA) Sequencing

Background information for Gaucher Disease (GBA) Sequencing:
Characteristics: Gaucher disease (GD) is a lysosomal storage disorder with phenotypes ranging from perinatal lethality to lack of symptoms. There are three GD subtypes. Type 1 GD manifests with bone disease, hepatosplenomegaly, anemia, thrombocytopenia, and lung disease but no central nervous system (CNS) involvement. Type 2 GD exhibits CNS symptoms before age 2 and rapidly progresses, resulting in death by age 4. Type 3 GD presents as early as age 2 with CNS symptoms that slowly progress resulting in death during the third or fourth decade.
Incidence: 1 in 900 Ashkenazi Jewish individuals; approximately 1 in 57,000 to 1 in 75,000 in general population.
Inheritance: Autosomal recessive.
Cause: Two pathogenic GBA variants on opposite chromosomes.
Clinical Sensitivity: 99 percent.
Methodology: Long-range PCR followed by bidirectional sequencing of all coding regions and intron-exon boundaries of the GBA gene.
Analytical Sensitivity and Specificity: Approximately 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region variants, deep intronic variants, large deletions/duplications/insertions, gene conversion, and complex gene events may not be detected.