Deletion/Insertion Mutation That Causes Biotinidase Deficiency May Result from the Formation of a Quasipalindromic Structure

• Published in: Human molecular genetics 1996-10, Vol.5 (10), p.1657-1661
• Main Authors: Pomponio, Robert J., Narasimhan, Vasant, Reynolds, Thomas R., Buck, Gregory A., Povirk, Lawrence F., Wolf, Barry
• Format: Article
• Language: English
• Subjects: Amidohydrolases - deficiency; Amidohydrolases - genetics; Base Sequence; Biotinidase; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 7; DNA, Complementary - analysis; DNA, Complementary - genetics; Exons - genetics; Gene Deletion; Homozygote; Humans; Infant; Male; Molecular Sequence Data; Nucleic Acid Conformation
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/5.10.1657

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 α. 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 α may preferentially arrest or dissociate at specific template sequences.