55-base pair deletion in certain patients with Gaucher disease complicates screening for common Gaucher alleles.

Mutations in the glucocerebrosidase gene which result in Gaucher disease can originate from the highly homologous glucocerebrosidase pseudogene. A 55-bp deletion in exon 9, which corresponds to a 55-bp segment absent from the pseudogene, has been identified in patients with Gaucher disease. We have developed a simple polymerase chain reaction (PCR)-based method to detect this 55-bp deletion, and have found this mutation in 3 of 75 DNA samples (4%) collected from patients with Gaucher disease. Commonly used PCR-based screening methods for specific Gaucher mutations frequently make use of primers either within or surrounding the 55-bp gap to selectively distinguish the glucocerebrosidase gene from the pseudogene. However, if the 55-bp deletion in exon 9 occurs, primers will either fail to produce an amplification product or will produce a shortened product which will be falsely attributed to the pseudogene. This could lead to inaccurate genotyping and genetic counseling for some Gaucher patients and their families. We therefore recommended that laboratories using PCR-based screening techniques involving primers in this region initially determine whether this 55-bp sequence is present.