Impact of premature stop codons on mRNA levels in infantile Sandhoff disease

Sandhoff disease is an autosomal recessive lysosomal storagedisease resulting from mutations of the HEXB gene encoding theßsubunit of ß-hexosaminidase A. Fibroblast lines fromfour patients with the infantile form of the disease were investigatedfor mutations by single strand conformation polymorphism analysisand direct sequencing of PCR products. Two of the cell lineswere homozygous for a common, 16 kb deletion of the 5’end of HEXB gene. The two other cell lines contained the 16kb deletion along with a second mutant allele generating a stopcodon: In one case a nonsense mutation, C₈₅₀—T, whichgenerated a stop codon at codon 284; and in the other, a singlebase deletion,