Human propionyl-CoA carboxylase beta subunit gene: exon-intron definition and mutation spectrum in Spanish and Latin American propionic acidemia patients.
Propionyl-CoA carboxylase (PCC) is a mitochondrial biotin-dependent enzyme composed of an equal number of alpha and beta subunits. Mutations in the PCCA (alpha subunit) or PCCB (beta subunit) gene can cause the inherited metabolic disease propionic acidemia (PA), which can be life threatening in the neonatal period. Lack of data on the genomic structure of PCCB has been a significant impediment to full characterization of PCCB mutant chromosomes. In this study, we describe the genomic organization of the coding sequence of the human PCCB gene and the characterization of mutations causing PA in a total of 29 unrelated patients-21 from Spain and 8 from Latin America. The implementation of long-distance PCR has allowed us to amplify the regions encompassing the exon/intron boundaries and all the exons. The gene consists of 15 exons of 57-183 bp in size. All splice sites are consistent with the gt/ag rule. The availability of the intron sequences flanking each exon has provided the basis for implementation of screening for mutations in the PCCB gene. A total of 56/58 mutant chromosomes studied have been defined, with a total of 16 different mutations detected. The mutation spectrum includes one insertion/deletion, two insertions, 10 missense mutations, one nonsense mutation, and two splicing defects. Thirteen of these mutations correspond to those not described yet in other populations. The mutation profile found in the chromosomes from the Latin American patients basically resembles that of the Spanish patients.
Rodríguez-Pombo
P
P
Departamento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa" Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, Spain.
Hoenicka
J
J
Muro
S
S
Pérez
B
B
Pérez-Cerdá
C
C
Richard
E
E
Desviat
L R
LR
Ugarte
M
M
D019943:Amino Acid Substitution; D001483:Base Sequence; D002262:Carboxy-Lyases / Q000737:chemistry / Q000235:genetics*; D002460:Cell Line; D018388:Codon, Terminator; D004251:DNA Transposable Elements; D005091:Exons; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D007843:Latin America; D046911:Macromolecular Substances; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D043586:Methylmalonyl-CoA Decarboxylase; D009154:Mutation; D009679:Nuclear Family; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011422:Propionates / Q000378:metabolism*; D017384:Sequence Deletion; D013030:Spain
D018388:Codon, Terminator; D004251:DNA Transposable Elements; D046911:Macromolecular Substances; D011422:Propionates; D002262:Carboxy-Lyases; D043586:Methylmalonyl-CoA Decarboxylase