title: Three independent mutations in the same exon of the PCCB gene: differences between Caucasian and Japanese propionic acidaemia.
abstract: Propionic acidaemia is an inborn error of organic acid metabolism caused by deficiency of propionyl-CoA carboxylase (PCC). Enzyme deficiency can result from mutations in either of the non-identical alpha- and beta-subunits. We have screened genomic DNA from patients with defects in the beta-subunit from two ethnic groups (Caucasians and Japanese) and detected three types of mutations in the same exon of the coding sequence of the beta-subunit: an insertion/deletion that replaces 14 nucleotides with 12 nucleotides of unrelated sequence and eliminates an Msp I site; a 3-bp deletion of a single isoleucine codon immediately proximal to that Msp I site; and a C-->T transition in the same Msp I site. The insertion/deletion was detected only in Caucasian patients in 11 of 34 mutant alleles; the C-->T transition was found only in Japanese patients in 4 of 12 mutant alleles. Following digestion of genomic DNA by Msp I, both of these mutations were detected on Southern blots by the presence of a 2.7-kbp band; they can be distinguished from one another by allele-specific oligonucleotide hybridization following PCR amplification. These results underscore the independent origin of the mutations in the two populations and suggest a key role of this exon in the beta-subunit of PCC.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06510.
authors.forename: T
authors.initials: T
authors.lastname: Tahara
authors.forename: J P
authors.initials: JP
authors.lastname: Kraus
authors.forename: T
authors.initials: T
authors.lastname: Ohura
authors.forename: L E
authors.initials: LE
authors.lastname: Rosenberg
authors.forename: W A
authors.initials: WA
authors.lastname: Fenton
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D002262:Carboxy-Lyases / Q000172:deficiency / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D006801:Humans; D007564:Japan; D043586:Methylmalonyl-CoA Decarboxylase; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011422:Propionates / Q000097:blood*; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*
chemical_list: D011422:Propionates; D004247:DNA; D002262:Carboxy-Lyases; D043586:Methylmalonyl-CoA Decarboxylase