title: [The human OCTN2 carnitine transporter and its mutations].
abstract: The gene currently known as SLC22A5 was already sequenced in the Human Genome project, and it was annotated as the gene of the high affinity carnitine transporter (OCTN2) in 1998. After the verification of the real function of the OCTN2 several disease related mutations of the gene have been identified, albeit the entity of the primary carnitine deficiency syndrome (OMIM 212140) was separated earlier. Besides the description of the biochemical characteristics of the transporter the present review gives a summary on the mutation spectrum and the developing phenotypes according to the literature available on the Medline and to own observations. The disease spectrum includes the involvement of the cardiac muscle and the liver primarily, however, a relatively wide phenotype variability has been observed even with the same mutations. Metabolic crisis or cardiac arrest can develop in homozygotes. Since the carnitine plays a regulatory role in the mitochondrial oxidation of the long chain fatty acids, loss of OCTN2 function lead to severe impairment of the intracellular metabolism at biochemical level, which can explain the development of a severe, even life threatening condition. The cardiac symptoms can be well influenced by carnitine administration. There are indications that cardiac manifestations can develop even in heterozygotes probably in association with the gene-dose relationship; in the laboratory of the author a heterozygous C-->T transition at the 15 np of the exon V of the OCTN2 in a patient with mild cardiomyopathy and ischemic heart disease was verified. This results in a serine 280 phenylalanine (S280F) exchange affecting thereby one of the putative protein C kinase dependent phosphorylation sites.
authors.affiliation: Pécsi Tudományegyetem, Altalános Orvostudományi Kar, Orvosi Genetikai és Gyermekfejlódéstani Intézet, Pécs. Bela.Melegh@aok.pte.hu
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
mesh_terms: D002331:Carnitine / Q000008:administration & dosage / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006323:Heart Arrest / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D027701:Organic Cation Transport Proteins; D010641:Phenotype; D000074058:Solute Carrier Family 22 Member 5
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine