Deletion/insertion mutation that causes biotinidase deficiency may result from the formation of a quasipalindromic structure.
Biotinidase is responsible for recycling the vitamin biotin from biocytin that is formed after the proteolytic degradation of the biotin-dependent carboxylases. We have identified a deletion/insertion mutation within exon D of the human biotinidase gene in a child with biotinidase deficiency. The mutation causes a frame shift and premature termination which are predicted to result in a truncated protein. We propose that the mutation occurred during DNA replication by either of two mechanisms. Both mechanisms involve formation of a quasipalindromic hairpin loop in the template and dissociation of DNA polymerase alpha. This mutation supports the formation of palindromic structures as a possible cause of deletions in eukaryotes, and supports the proposal, derived from in vitro studies, that polymerase alpha may preferentially arrest or dissociate at specific template sequences.
Human Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.
R J
RJ
Pomponio
V
V
Narasimhan
T R
TR
Reynolds
G A
GA
Buck
L F
LF
Povirk
B
B
Wolf
D000581:Amidohydrolases / Q000172:deficiency* / Q000235:genetics; D001483:Base Sequence; D043523:Biotinidase; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation
D018076:DNA, Complementary; D000581:Amidohydrolases; D043523:Biotinidase