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Title: An unusual insertion/deletion in the gene encoding the. beta. -subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia

Abstract

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 thismore » position or, more likely, the mutations in all of the involved Caucasian patients have a common origin in preceding generations.« less

Authors:
; ;  [1]
  1. Yale Univ. School of Medicine, New Haven, CT (USA)
Publication Date:
OSTI Identifier:
6172274
Resource Type:
Journal Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America; (USA)
Additional Journal Information:
Journal Volume: 87:4; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 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

Citation Formats

Tahara, T, Kraus, J P, and Rosenberg, L E. An unusual insertion/deletion in the gene encoding the. beta. -subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia. United States: N. p., 1990. Web. doi:10.1073/pnas.87.4.1372.
Tahara, T, Kraus, J P, & Rosenberg, L E. An unusual insertion/deletion in the gene encoding the. beta. -subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia. United States. doi:10.1073/pnas.87.4.1372.
Tahara, T, Kraus, J P, and Rosenberg, L E. Thu . "An unusual insertion/deletion in the gene encoding the. beta. -subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia". United States. doi:10.1073/pnas.87.4.1372.
@article{osti_6172274,
title = {An unusual insertion/deletion in the gene encoding the. beta. -subunit of propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic acidemia},
author = {Tahara, T and Kraus, J P and Rosenberg, L E},
abstractNote = {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.},
doi = {10.1073/pnas.87.4.1372},
journal = {Proceedings of the National Academy of Sciences of the United States of America; (USA)},
issn = {0027-8424},
number = ,
volume = 87:4,
place = {United States},
year = {1990},
month = {2}
}