Functional analysis of mutations in the OCTN2 transporter causing primary carnitine deficiency: Lack of genotype-phenotype correlation

Yuhuan Wang, Franco Taroni, Barbara Garavaglia, Nicola Longo

Research output: Contribution to journalArticle

Abstract

Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation caused by defective carnitine transport. This disease is caused by mutations in the novel organic cation transporter OCTN2 (SLC22A5 gene). The disease can present early in life with hypoketotic hypoglycemia or later in life with skeletal myopathy or cardiomyopathy. To determine whether the variation in phenotypic severity is due to mutations retaining residual function, we extended mutational analysis of OCTN2 to four additional European families with primary carnitine deficiency. Three patients were homozygous for novel missense mutations (R169W, G242V, A301D). The fourth patient was compound heterozygous for R169W and W351R substitutions. Stable expression of all the mutations in CHO cells confirmed that all mutations abolished carnitine transport, with the exception of the A301D mutation in which residual carnitine transport was 23% of the value measured in cells expressing the normal OCTN2 cDNA. Analysis of the patients characterized in molecular detail by our laboratory failed to indicate a correlation between residual carnitine transport and severity of the phenotype or age at presentation. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)401-407
Number of pages7
JournalHuman Mutation
Volume16
Issue number5
DOIs
Publication statusPublished - 2000

Keywords

  • Cardiomyopathy
  • Carnitine deficiency
  • Carnitine transport
  • Fatty acid oxidation
  • OCTN2
  • SLC22A5

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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