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Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency.
Proc Natl Acad Sci U S A. 1999 Mar 02; 96(5):2356-60.PN

Abstract

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

Authors+Show Affiliations

Division of Medical Genetics, Department of Pediatrics, Emory University, 2040 Ridgewood Drive, Atlanta, GA 30322, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10051646

Citation

Wang, Y, et al. "Mutations in the Organic Cation/carnitine Transporter OCTN2 in Primary Carnitine Deficiency." Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 5, 1999, pp. 2356-60.
Wang Y, Ye J, Ganapathy V, et al. Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. Proc Natl Acad Sci U S A. 1999;96(5):2356-60.
Wang, Y., Ye, J., Ganapathy, V., & Longo, N. (1999). Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. Proceedings of the National Academy of Sciences of the United States of America, 96(5), 2356-60.
Wang Y, et al. Mutations in the Organic Cation/carnitine Transporter OCTN2 in Primary Carnitine Deficiency. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2356-60. PubMed PMID: 10051646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. AU - Wang,Y, AU - Ye,J, AU - Ganapathy,V, AU - Longo,N, PY - 1999/3/3/pubmed PY - 1999/3/3/medline PY - 1999/3/3/entrez SP - 2356 EP - 60 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 96 IS - 5 N2 - Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation caused by defective carnitine transport. This disease presents early in life with hypoketotic hypoglycemia or later in life with skeletal myopathy or cardiomyopathy. The gene for this condition maps to 5q31.2-32 and OCTN2, an organic cation/carnitine transporter, also maps to the same chromosomal region. Here we test the causative role of OCTN2 in primary carnitine deficiency by searching for mutations in this gene in affected patients. Fibroblasts from patients with primary carnitine deficiency lacked mediated carnitine transport. Transfection of patient's fibroblasts with the OCTN2 cDNA partially restored carnitine transport. Sequencing of the OCTN2 gene revealed different mutations in two unrelated patients. The first patient was homozygous (and both parents heterozygous) for a single base pair substitution converting the codon for Arg-282 to a STOP codon (R282X). The second patient was a compound heterozygote for a paternal 1-bp insertion producing a STOP codon (Y401X) and a maternal 1-bp deletion that produced a frameshift creating a subsequent STOP codon (458X). These mutations decreased the levels of mature OCTN2 mRNA and resulted in nonfunctional transporters, confirming that defects in the organic cation/carnitine transporter OCTN2 are responsible for primary carnitine deficiency. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/10051646/Mutations_in_the_organic_cation/carnitine_transporter_OCTN2_in_primary_carnitine_deficiency_ DB - PRIME DP - Unbound Medicine ER -