Different somatic and germline HPRT1 mutations promote use of a common, cryptic intron 1 splice site. Mutation in brief no. 259. Online.

Aberrant hypoxanthine phosphoribosyltransferase (HUGO-approved gene symbol HPRT1; MIM# 308000) RNA splicing promoted by splice site mutation or loss is a common mechanism for loss of the purine salvage enzyme HPRT1 from human cells. We report here two in vivo somatic HPRT1 mutations in human kidney tubular epithelial cells that disrupt HPRT1 intron 1 splicing and lead to the inclusion of intron 1 sequence in mature mRNA. Analysis of these mutations and of 14 additional HPRT1 intron 1 inclusion mutations provides an explanation for use of a common, cryptic intron 1 splice donor site by all 16 mutations.