An unusual insertion/deletion in the gene encoding the. beta. -subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia
- Yale Univ. School of Medicine, New Haven, CT (USA)
Propionic acidemia is an inherited disorder of organic acid metabolism that is caused by deficiency of propionly-CoA carboxylase. Affected patients fall into two complementation groups, pccA and pccBC (subgroups B, C, and BC), resulting from deficiency of the nonidentical {alpha} and {beta} subunits of PCC, respectively. The authors have detected an unusual insertion/deletion in the DNA of patients from the pccBC and pccC subgroups that replaces 14 nucleotides in the coding sequence of the {beta} subunit with 12 nucleotides unrelated to this region of the gene. Among 14 unrelated Caucasian patients in the pccBc complementation group, this unique mutation was found in 8 of 28 mutant alleles examined. Mutant allele-specific oligonucleotide hybridization to amplified genomic DNAs revealed that the inserted 12 nucleotides do not originate in an {approx}1000-bp region around the mutation. In the course of the investigation, they identified another mutation in the same exon: a 3-bp in-frame deletion that eliminates one of two isoleucine codons immediately preceding the Msp I site. Two unrelated patients were compound heterozygotes for this single-codon deletion and for the insertion/deletion described above. They conclude that either there is a propensity for the PCC {beta}-subunit gene to undergo mutations of this sort at this position or, more likely, the mutations in all of the involved Caucasian patients have a common origin in preceding generations.
- OSTI ID:
- 6172274
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:4; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
GENE MUTATIONS
DNA SEQUENCING
HEREDITARY DISEASES
PATHOGENESIS
LIGASES
AMINO ACID SEQUENCE
DNA
DNA HYBRIDIZATION
MESSENGER-RNA
METABOLIC DISEASES
OLIGONUCLEOTIDES
PATIENTS
PHOSPHORUS 32
TRANSCRIPTION
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DISEASES
ENZYMES
HYBRIDIZATION
ISOTOPES
LIGHT NUCLEI
MOLECULAR STRUCTURE
MUTATIONS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RNA
STRUCTURAL CHEMICAL ANALYSIS
550201* - Biochemistry- Tracer Techniques