PMID- 10425211
OWN - NLM
STAT- MEDLINE
DCOM- 19990908
LR  - 20171116
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 261
IP  - 2
DP  - 1999 Aug 2
TI  - Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a
      novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an
      unconventional splicing abnormality.
PG  - 484-7
AB  - Systemic primary carnitine deficiency (CDSP, MIM 212140) is a disorder of fatty
      acid oxidation manifesting in acute metabolic decompensation or in progressive
      cardiomyopathy and muscle weakness. Mutations in the plasmalemmal organic
      cation/carnitine transporter OCTN2 were recently identified in CDSP patients of
      diverse ethnic backgrounds. We have performed OCTN2 mutation analysis in two
      unrelated German patients with primary carnitine deficiency and identified three 
      molecular abnormalities. On one of the four chromosomes analyzed, we detected an 
      Arg169Gln missense mutation that affects an arginine residue absolutely conserved
      in the entire transporter superfamily to which OCTN2 belongs. On the three other 
      chromosomes, we found an Arg282ter nonsense mutation in exon 5. This mutation is 
      embedded into different haplotypes of closely spaced intragenic dimorphisms in
      our two patients and was recently described in a patient of Asiatic Indian
      background, so it appears to be a recurrent or ancient founder mutation that may 
      account for more CDSP cases. Finally, we found that the Arg282ter nonsense
      mutation is associated with a splicing abnormality at the intron 6/exon 7
      junction. However, no mutations are present in exon 6, intron 6, or exon 7,
      suggesting that defective splicing of exon 7 on the Arg282ter allele is due to an
      unconventional, long-distance mechanism.
CI  - Copyright 1999 Academic Press.
FAU - Burwinkel, B
AU  - Burwinkel B
AD  - Institut fur Physiologische Chemie, Ruhr-Universitat Bochum, Bochum, D-44780,
      Germany.
FAU - Kreuder, J
AU  - Kreuder J
FAU - Schweitzer, S
AU  - Schweitzer S
FAU - Vorgerd, M
AU  - Vorgerd M
FAU - Gempel, K
AU  - Gempel K
FAU - Gerbitz, K D
AU  - Gerbitz KD
FAU - Kilimann, M W
AU  - Kilimann MW
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Carrier Proteins)
RN  - 0 (Codon, Nonsense)
RN  - 0 (DNA Primers)
RN  - 0 (Membrane Proteins)
RN  - 0 (Organic Cation Transport Proteins)
RN  - 0 (SLC22A5 protein, human)
RN  - 0 (Solute Carrier Family 22 Member 5)
RN  - 9007-49-2 (DNA)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
MH  - Adolescent
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Carnitine/*deficiency/metabolism
MH  - Carrier Proteins/*genetics/metabolism
MH  - Child
MH  - Child, Preschool
MH  - Codon, Nonsense
MH  - DNA/genetics
MH  - DNA Primers/genetics
MH  - Exons
MH  - Humans
MH  - Introns
MH  - Male
MH  - Membrane Proteins/*genetics/metabolism
MH  - *Mutation
MH  - Mutation, Missense
MH  - *Organic Cation Transport Proteins
MH  - Point Mutation
MH  - RNA Splicing/genetics
MH  - Sequence Deletion
MH  - Solute Carrier Family 22 Member 5
EDAT- 1999/07/30 00:00
MHDA- 1999/07/30 00:01
CRDT- 1999/07/30 00:00
PHST- 1999/07/30 00:00 [pubmed]
PHST- 1999/07/30 00:01 [medline]
PHST- 1999/07/30 00:00 [entrez]
AID - 10.1006/bbrc.1999.1060 [doi]
AID - S0006-291X(99)91060-4 [pii]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Aug 2;261(2):484-7. doi: 10.1006/bbrc.1999.1060.