PMID- 10545605
OWN - NLM
STAT- MEDLINE
DCOM- 19991214
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 12
DP  - 1999 Nov
TI  - Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese
      population and phenotypic characterization in Japanese pedigrees with primary
      systemic carnitine deficiency.
PG  - 2247-54
AB  - Serum free-carnitine levels were determined in 973 unrelated white collar workers
      in Akita, Japan. Fourteen of these participants consistently had serum
      free-carnitine levels below the fifth percentile (28 microM for females and 38
      microM for males). The OCTN2 (organic cation transporter) gene was sequenced for 
      these 14 subjects, for 22 subjects whose carnitine levels were below the fifth
      percentile in the first screening but were normal in the second measurement and
      in 69 individuals with normal carnitine levels for two separate measurements.
      Polymorphic sequences defined three major haplotypes with equal frequency.
      Mutations were identified in nine subjects with low carnitine levels: Trp132X
      (three individuals), Ser467Cys (four), Trp283Cys (one) and Met179Leu (one). In
      vitro expression studies in HEK cells indicated that Ser467Cys and Trp283Cys, but
      not Met179Leu, significantly reduced L-carnitine uptake relative to the normal
      control. Trp132X and Ser467Cys were associated with specific haplotypes,
      suggesting a founder effect. A conservative estimate of the overall prevalence of
      heterozygotes was 1.01% in the Akita prefecture, Japan, giving an estimated
      incidence of primary systemic carnitine deficiency (MIM 212140) as 1 in 40 000
      births. An echocardiographic study of the families of patients with primary
      carnitine deficiency revealed that the heterozygotes for OCTN2 mutations were
      predisposed to late onset benign cardiac hypertrophy (odds ratio 15.1, 95% CI
      1.39-164) compared with the wild-types. Sequencing of DNA isolated from three
      deceased siblings (1.5-8 years) in two families retrospectively confirmed that
      all three deceased subjects were homozygous for the OCTN2 mutations.
FAU - Koizumi, A
AU  - Koizumi A
AD  - Department of Hygiene, Akita University School of Medicine, Akita 010-8543,
      Japan. koizumi@med.akita-u.ac.jp
FAU - Nozaki, J
AU  - Nozaki J
FAU - Ohura, T
AU  - Ohura T
FAU - Kayo, T
AU  - Kayo T
FAU - Wada, Y
AU  - Wada Y
FAU - Nezu, J
AU  - Nezu J
FAU - Ohashi, R
AU  - Ohashi R
FAU - Tamai, I
AU  - Tamai I
FAU - Shoji, Y
AU  - Shoji Y
FAU - Takada, G
AU  - Takada G
FAU - Kibira, S
AU  - Kibira S
FAU - Matsuishi, T
AU  - Matsuishi T
FAU - Tsuji, A
AU  - Tsuji A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Carrier Proteins)
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  - Base Sequence
MH  - Carnitine/*metabolism
MH  - Carrier Proteins/*genetics/metabolism
MH  - DNA
MH  - Female
MH  - Humans
MH  - Japan
MH  - Male
MH  - Membrane Proteins/*genetics/metabolism
MH  - *Molecular Epidemiology
MH  - Mutagenesis, Site-Directed
MH  - *Organic Cation Transport Proteins
MH  - Pedigree
MH  - Phenotype
MH  - Solute Carrier Family 22 Member 5
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - ddc253 [pii]
AID - 10.1093/hmg/8.12.2247 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Nov;8(12):2247-54. doi: 10.1093/hmg/8.12.2247.