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Title: Mutations participating in interallelic complementation in propionic acidemia

Abstract

Deficiency of propionyl-CoA carboxylase (PCC; [alpha][sub 4][beta][sub 4]) results in the rare, autosomal recessive disease propionic acidemia. Cell fusion experiments have revealed two complementation groups, pccA and pccB, corresponding to defects of the PCCA ([alpha]-subunit) and PCCB ([beta]-subunit) genes, respectively. The pccBCC group includes subgroups, pccB and pccC, which are thought to reflect interallelic complementation between certain mutations of the PCCB gene. In this study, the authors have identified the mutations in two pccB, one pccC, and two pccBC cell lines and have deduced those alleles participating in interallelic complementation. One pccB line was a compound hetrozygote of Pro228Leu and Asn536Asp. The latter mutation was also detected in a noncomplementing pccBC line. This leaves Pro228Leu responsible for complementation in the pccB cells. The second pccB line contained an insertional duplication, dupKICK140-143, and a splice mutation IVS+1 G[yields]T, located after Lys466. The authors suggest that the dupKICK mutation is the complementing allele, since the second allele is incompatible with normal splicing. The pccC line studied was homozygous for Arg410Trp, which is necessarily the complementing allele in that line. For a second pccC line, they previously had proposed that [Delta]Ile408 was the complementing allele. They now show that its second allele, [openmore » quotes]Ins[center dot]Del[close quotes], a 14-bp deletion replaced by a 12-bp insertion beginning at codon 407, fails to complement in homozygous form. The authors conclude that the interallelic complementation results from mutations in domains that can interact between [beta]-subunits in the PCC heteromer to restore enzymatic function. On the basis of sequence homology with the Propionibacterium shermanii transcarboxylase 12S subunit, they suggest that the pccC domain, defined by Ile408 and Arg410, may involve the propionyl-CoA binding site. 37 refs., 5 figs., 2 tabs.« less

Authors:
; ; ; ; ;  [1]
  1. McGill Univ., Montreal (Canada)
Publication Date:
OSTI Identifier:
6821838
Resource Type:
Journal Article
Journal Name:
American Journal of Human Genetics; (United States)
Additional Journal Information:
Journal Volume: 55:1; Journal ID: ISSN 0002-9297
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CARBOXYLASE; GENE MUTATIONS; DETECTION; PROPIONIC ACID; METABOLIC DISEASES; CARBON-CARBON LYASES; CARBOXY-LYASES; CARBOXYLIC ACIDS; DISEASES; ENZYMES; LYASES; MONOCARBOXYLIC ACIDS; MUTATIONS; ORGANIC ACIDS; ORGANIC COMPOUNDS; PROTEINS; 550400* - Genetics

Citation Formats

Gravel, R A, Akerman, B R, Lamhonwah, A M, Loyer, M, Leon-del-Rio, A, and Italiano, I. Mutations participating in interallelic complementation in propionic acidemia. United States: N. p., 1994. Web.
Gravel, R A, Akerman, B R, Lamhonwah, A M, Loyer, M, Leon-del-Rio, A, & Italiano, I. Mutations participating in interallelic complementation in propionic acidemia. United States.
Gravel, R A, Akerman, B R, Lamhonwah, A M, Loyer, M, Leon-del-Rio, A, and Italiano, I. Fri . "Mutations participating in interallelic complementation in propionic acidemia". United States.
@article{osti_6821838,
title = {Mutations participating in interallelic complementation in propionic acidemia},
author = {Gravel, R A and Akerman, B R and Lamhonwah, A M and Loyer, M and Leon-del-Rio, A and Italiano, I},
abstractNote = {Deficiency of propionyl-CoA carboxylase (PCC; [alpha][sub 4][beta][sub 4]) results in the rare, autosomal recessive disease propionic acidemia. Cell fusion experiments have revealed two complementation groups, pccA and pccB, corresponding to defects of the PCCA ([alpha]-subunit) and PCCB ([beta]-subunit) genes, respectively. The pccBCC group includes subgroups, pccB and pccC, which are thought to reflect interallelic complementation between certain mutations of the PCCB gene. In this study, the authors have identified the mutations in two pccB, one pccC, and two pccBC cell lines and have deduced those alleles participating in interallelic complementation. One pccB line was a compound hetrozygote of Pro228Leu and Asn536Asp. The latter mutation was also detected in a noncomplementing pccBC line. This leaves Pro228Leu responsible for complementation in the pccB cells. The second pccB line contained an insertional duplication, dupKICK140-143, and a splice mutation IVS+1 G[yields]T, located after Lys466. The authors suggest that the dupKICK mutation is the complementing allele, since the second allele is incompatible with normal splicing. The pccC line studied was homozygous for Arg410Trp, which is necessarily the complementing allele in that line. For a second pccC line, they previously had proposed that [Delta]Ile408 was the complementing allele. They now show that its second allele, [open quotes]Ins[center dot]Del[close quotes], a 14-bp deletion replaced by a 12-bp insertion beginning at codon 407, fails to complement in homozygous form. The authors conclude that the interallelic complementation results from mutations in domains that can interact between [beta]-subunits in the PCC heteromer to restore enzymatic function. On the basis of sequence homology with the Propionibacterium shermanii transcarboxylase 12S subunit, they suggest that the pccC domain, defined by Ile408 and Arg410, may involve the propionyl-CoA binding site. 37 refs., 5 figs., 2 tabs.},
doi = {},
journal = {American Journal of Human Genetics; (United States)},
issn = {0002-9297},
number = ,
volume = 55:1,
place = {United States},
year = {1994},
month = {7}
}