Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency

摘要: Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation caused by defective transport. This disease presents early in life with hypoketotic hypoglycemia or later skeletal myopathy cardiomyopathy. The gene for this condition maps to 5q31.2–32 and OCTN2, organic cation/carnitine transporter, also the same chromosomal region. Here we test causative role OCTN2 primary searching mutations affected patients. Fibroblasts from patients lacked mediated Transfection patient’s fibroblasts cDNA partially restored Sequencing revealed different two unrelated first patient was homozygous (and both parents heterozygous) a single base pair substitution converting codon Arg-282 STOP (R282X). second compound heterozygote paternal 1-bp insertion producing (Y401X) maternal deletion that produced frameshift creating subsequent (458X). These decreased levels mature mRNA resulted nonfunctional transporters, confirming defects transporter are responsible deficiency.