title: Phenotype and genotype variation in primary carnitine deficiency.
abstract: OBJECTIVE
  Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation resulting from defective carnitine transport. This disease is caused by mutations in the carnitine transporter gene SLC22A5. The objective of this study was to extend mutational analysis to four additional families with this disorder and determine whether recurrent mutations could be found.
  
  
  METHODS
  The SLC22A5 gene encoding the OCTN2 carnitine transporter was sequenced, and the missense mutations identified were expressed in Chinese hamster ovary (CHO) cells.
  
  
  RESULTS
  DNA sequencing revealed four novel mutations (Y4X; dup 254-264, 133X; R19P; R399Q). Alleles introducing premature STOP codons reduced the levels of OCTN2 mRNA. Carnitine transport in CHO cells expressing the R19P and R399Q mutations was reduced to < 5% of normal. The 133X mutation was found in two unrelated European families. Two patients within the same family, both homozygous for the same mutation (R399Q) had completely different clinical presentation.
  
  
  CONCLUSIONS
  Heterogeneous mutations in the SLC22A5 gene cause primary carnitine deficiency. Different presentations are observed even in children with identical mutations.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: S H
authors.initials: SH
authors.lastname: Korman
authors.forename: J
authors.initials: J
authors.lastname: Ye
authors.forename: J J
authors.initials: JJ
authors.lastname: Gargus
authors.forename: A
authors.initials: A
authors.lastname: Gutman
authors.forename: F
authors.initials: F
authors.lastname: Taroni
authors.forename: B
authors.initials: B
authors.lastname: Garavaglia
authors.forename: N
authors.initials: N
authors.lastname: Longo
mesh_terms: D000818:Animals; D016466:CHO Cells; D002331:Carnitine / Q000172:deficiency* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D006224:Cricetinae; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D027701:Organic Cation Transport Proteins; D010641:Phenotype; D017422:Sequence Analysis, DNA; D012867:Skin / Q000166:cytology; D000074058:Solute Carrier Family 22 Member 5
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine