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.
Pomponio
R J
RJ
Human Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.
Narasimhan
V
V
Reynolds
T R
TR
Buck
G A
GA
Povirk
L F
LF
Wolf
B
B
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