Gaucher Disease (GBA), 8 Variants

Background information for Gaucher Disease (GBA), 8 Variants:
Characteristics: Gaucher disease affects lysosomal storage and has extreme symptom variability, ranging from perinatal lethality to asymptomatic individuals. Three Gaucher subtypes have been identified based on symptom characteristics. Type 1 is characterized by bone disease, hepatosplenomegaly, anemia, thrombocytopenia, and lung disease. Individuals with Type 1 disease do not have primary central nervous system (CNS) involvement. Type 2 is characterized by CNS symptoms displaying before age 2, which progresses rapidly resulting in death by age 4. In Type 3 disease, individuals may present as early as age 2 with display CNS symptoms. However, Type 3 disease progresses slowly, usually resulting in death during the third or fourth decade of life.
Incidence: 1 in 900 in Ashkenazi Jewish individuals.
Inheritance: Autosomal recessive.
Cause: GBA pathogenic variants.
Variants Tested: c.115+1G>A, p.L29Afs (c.84dupG), p.N409S (c.1226A>G), c.1263_1317del55, p.V433L (c.1297G>T), p.D448H (c.1342G>C), p.L483P (c.1448T>C), and p.R535H (c.1604G>A).
Clinical Sensitivity: 90 percent in Ashkenazi Jewish individuals; 55 percent in other ethnicities.
Methodology: Polymerase chain reaction (PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity: Greater than 99 percent.
Limitations: Variants other than those tested will not be detected. Diagnostic errors can occur due to rare sequence variations.