DELETION INSERTION MUTATION THAT CAUSES BIOTINIDASE DEFICIENCY MAY RESULT FROM THE FORMATION OF A QUASI-PALINDROMIC STRUCTURE/

Biotinidase is responsible for recycling the vitamin biotin from biocy tin that is formed after the proteolytic degradation of the biotin-dep endent carboxylases. We have identified a deletion/insertion mutation within exon D of the human biotinidase gene in a child with biotinidas e deficiency, The mutation causes a frame shift and premature terminat ion which are predicted to result in a truncated protein, We propose t hat the mutation occurred during DNA replication by either of two mech anisms, Both mechanisms involve formation of a quasipalindromic hairpi n loop in the template and dissociation of DNA polymerase alpha. This mutation supports the formation of palindromic structures as a possibl e cause of deletions in eukaryotes, and supports the proposal, derived from in vitro studies, that polymerase alpha may preferentially arres t or dissociate at specific template sequences.