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Three independent mutations in the same exon of the PCCB gene: Differences between Caucasian and Japanese propionic acidaemia
Author(s) -
Tahara T.,
Kraus J. P.,
Ohura T.,
Rosenberg L. E.,
Fenton W. A.
Publication year - 1993
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf00710282
Subject(s) - exon , genetics , biology , microbiology and biotechnology , transition (genetics) , genomic dna , coding region , gene , allele , mutant , mutation , stop codon , point mutation
Summary 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 α‐ and β‐subunits. We have screened genomic DNA from patients with defects in the β‐subunit from two ethnic groups (Caucasians and Japanese) and detected three types of mutations in the same exon of the coding sequence of the β‐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 β‐subunit of PCC.