title: A polymerase chain reaction-based genotyping assay for detecting a novel Sandhoff disease-causing mutation.
abstract: 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.
authors.affiliation: Department of Biology, University of Regina, Regina, Saskatchewan, Canada. braden.fitterer@health.gov.sk.ca
authors.forename: Braden B
authors.initials: BB
authors.lastname: Fitterer
authors.forename: Nick A
authors.initials: NA
authors.lastname: Antonishyn
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Hall
authors.forename: Denis C
authors.initials: DC
authors.lastname: Lehotay
mesh_terms: D000328:Adult; D005091:Exons / Q000235:genetics; D005823:Genetics; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D012497:Sandhoff Disease / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D012525:Saskatchewan / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D054821:beta-Hexosaminidase beta Chain / Q000235:genetics*
chemical_list: C513386:HEXB protein, human; D054821:beta-Hexosaminidase beta Chain