PMID- 10101253
OWN - NLM
STAT- MEDLINE
DCOM- 19990527
LR  - 20191210
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1453
IP  - 3
DP  - 1999 Mar 30
TI  - Genetic heterogeneity in propionic acidemia patients with alpha-subunit defects. 
      Identification of five novel mutations, one of them causing instability of the
      protein.
PG  - 351-8
AB  - The inherited metabolic disease propionic acidemia (PA) can result from mutations
      in either of the genes PCCA or PCCB, which encode the alpha and beta subunits,
      respectively, of the mitochondrial enzyme propionyl CoA-carboxylase. In this work
      we have analyzed the molecular basis of PCCA gene defects, studying mRNA levels
      and identifying putative disease causing mutations. A total of 10 different
      mutations, none predominant, are present in a sample of 24 mutant alleles
      studied. Five novel mutations are reported here for the first time. A neutral
      polymorphism and a variant allele present in the general population were also
      detected. To examine the effect of a point mutation (M348K) involving a highly
      conserved residue, we have carried out in vitro expression of normal and mutant
      PCCA cDNA and analyzed the mitochondrial import and stability of the resulting
      proteins. Both wild-type and mutant proteins were imported into mitochondria and 
      processed into the mature form with similar efficiency, but the mature mutant
      M348K protein decayed more rapidly than did the wild-type, indicating a reduced
      stability, which is probably the disease-causing mechanism.
FAU - Richard, E
AU  - Richard E
AD  - Departamento de Biologia Molecular and Centro de Biologia Molecular 'Severo
      Ochoa', CSIC-UAM, Universidad Autonoma de Madrid, 28049, Madrid, Spain.
FAU - Desviat, L R
AU  - Desviat LR
FAU - Perez, B
AU  - Perez B
FAU - Perez-Cerda, C
AU  - Perez-Cerda C
FAU - Ugarte, M
AU  - Ugarte M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Codon, Nonsense)
RN  - 0 (DNA, Complementary)
RN  - 0 (Propionates)
RN  - EC 4.1.1.- (Carboxy-Lyases)
RN  - EC 7.2.4.3 (Methylmalonyl-CoA Decarboxylase)
RN  - JHU490RVYR (propionic acid)
SB  - IM
MH  - Acid-Base Imbalance/blood/*genetics
MH  - Animals
MH  - Blotting, Northern
MH  - Carboxy-Lyases/biosynthesis/*deficiency/genetics
MH  - Cloning, Molecular
MH  - Codon, Nonsense
MH  - DNA, Complementary/biosynthesis
MH  - Humans
MH  - Methylmalonyl-CoA Decarboxylase
MH  - Mitochondria, Liver/metabolism
MH  - *Mutation
MH  - Propionates/*blood
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 1999/04/02 00:00
MHDA- 1999/04/02 00:01
CRDT- 1999/04/02 00:00
PHST- 1999/04/02 00:00 [pubmed]
PHST- 1999/04/02 00:01 [medline]
PHST- 1999/04/02 00:00 [entrez]
AID - S0925-4439(99)00008-3 [pii]
AID - 10.1016/s0925-4439(99)00008-3 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1999 Mar 30;1453(3):351-8. doi:
      10.1016/s0925-4439(99)00008-3.