Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency.

Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal recessive disease characterized by low serum and intracellular concentrations of carnitine. CDSP may present with acute metabolic derangement simulating Reye's syndrome within the first 2 years of life. After 3 years of age, patients with CDSP may present with cardiomyopathy and muscle weakness. A linkage with D5S436 in 5q was reported in a family. A recently cloned homologue of the organic cation transporter, OCTN2, which has sodium-dependent carnitine uptake properties, was also mapped to the same locus. We screened for mutation in OCTN2 in a confirmed CDSP family. One truncating mutation (Trp132Stop) and one missense mutation (Pro478Leu) of OCTN2 were identified together with two silent polymorphisms. Expression of the mutant cDNAs revealed virtually no uptake activity for both mutations. Our data indicate that mutations in OCTN2 are responsible for CDSP. Identification of the underlying gene in this disease will allow rapid detection of carriers and postnatal diagnosis of affected patients.
AuthorsN L Tang, V Ganapathy, X Wu, J Hui, P Seth, P M Yuen, R J Wanders, T F Fok, N M Hjelm
JournalHuman molecular genetics (Hum Mol Genet) Vol. 8 Issue 4 Pg. 655-60 (Apr 1999) ISSN: 0964-6906 [Print] ENGLAND
PMID10072434 (Publication Type: Journal Article)
Chemical References
  • Carrier Proteins
  • Membrane Proteins
  • Organic Cation Transport Proteins
  • Recombinant Fusion Proteins
  • SLC22A5 protein, human
  • Carnitine
  • Amino Acid Sequence
  • Biological Transport (genetics)
  • Carnitine (deficiency, pharmacokinetics)
  • Carrier Proteins (genetics)
  • Cell Line
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Gene Expression Regulation
  • Genotype
  • Humans
  • Male
  • Membrane Proteins (genetics)
  • Molecular Sequence Data
  • Mutation
  • Organic Cation Transport Proteins
  • Pedigree
  • Recombinant Fusion Proteins (genetics)
  • Sequence Alignment
  • Sequence Homology, Amino Acid

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