A polymerase chain reaction-based genotyping assay for detecting a novel Sandhoff disease-causing mutation

Sandhoff disease is a rare genetic disorder, however, some northern Saskatchewan communities have a high incidence of the disease (for which the causative mutation has not been described). We discovered a novel mutation causing Sandhoff disease in this community and validated a molecular assay to detect the mutant allele. DNA sequencing was used to search for mutations in the HEXB gene from the most recently affected patient. A polymerase chain reaction (PCR)-based genotyping assay was subsequently designed and validated to detect a novel single-nucleotide deletion using DNA isolated from newborn screening cards. The c.115delG mutation was found in exon 1 of the HEXB gene from 4 patients with clinical presentation of Sandhoff disease. Herein we describe a novel HEXB mutation that is shared among 4 patients with Sandhoff disease, as well as a validated PCR-based genotyping assay that can reliably detect the mutant allele. Because the 4 patients from this community share a common c.115delG mutation in the coding region of the HEXB gene, it may be possible to offer an effective preventive screening program for Sandhoff disease using this assay.