title: Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency.
abstract: Systemic carnitine deficiency is a potentially lethal, autosomal recessive disorder characterized by cardiomyopathy, myopathy, recurrent episodes of hypoketotic hypoglycemia, hyperammonemia, and failure to thrive. This form of carnitine deficiency is caused by a defect in the active cellular uptake of carnitine, and the gene encoding the high affinity carnitine transporter OCTN2 has recently been shown to be mutated in patients suffering from this disorder. Here, we report the underlying molecular defect in three unrelated patients. Two patients were homozygous for the same missense mutation 632A-->G, which changes the tyrosine at amino acid position 211 into a cysteine (Y211C). The third patient was homozygous for a nonsense mutation, 844C-->T, which converts the arginine at amino acid position 282 into a stop codon (R282X). Reintroduction of wild-type OCTN2 cDNA into fibroblasts of the three patients by transient transfection restored the cellular carnitine uptake, confirming that mutations in OCTN2 are the cause of systemic carnitine deficiency.
authors.affiliation: Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: F M
authors.initials: FM
authors.lastname: Vaz
authors.forename: H R
authors.initials: HR
authors.lastname: Scholte
authors.forename: J
authors.initials: J
authors.lastname: Ruiter
authors.forename: L M
authors.initials: LM
authors.lastname: Hussaarts-Odijk
authors.forename: R R
authors.initials: RR
authors.lastname: Pereira
authors.forename: S
authors.initials: S
authors.lastname: Schweitzer
authors.forename: J B
authors.initials: JB
authors.lastname: de Klerk
authors.forename: H R
authors.initials: HR
authors.lastname: Waterham
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
mesh_terms: D001483:Base Sequence; D002331:Carnitine / Q000172:deficiency* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D005347:Fibroblasts; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D027701:Organic Cation Transport Proteins; D010641:Phenotype; D017354:Point Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074058:Solute Carrier Family 22 Member 5; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine