Phenotype and genotype variation in primary carnitine deficiency

Yuhuan Wang, Stanley H. Korman, Jing Ye, J. Jay Gargus, Alisa Gutman, Franco Taroni, Barbara Garavaglia, Nicola Longo

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Purpose: 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.

Original languageEnglish
Pages (from-to)387-392
Number of pages6
JournalGenetics in Medicine
Volume3
Issue number6
Publication statusPublished - 2001

Fingerprint

Genotype
Phenotype
Mutation
Carnitine
Cricetulus
Ovary
Genes
Systemic carnitine deficiency
Missense Mutation
DNA Sequence Analysis
Codon
Fatty Acids
Alleles
Messenger RNA

Keywords

  • Cardiomyopathy
  • Carnitine deficiency
  • Developmental delay
  • Fatty acid oxidation
  • OCTN2

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Wang, Y., Korman, S. H., Ye, J., Gargus, J. J., Gutman, A., Taroni, F., ... Longo, N. (2001). Phenotype and genotype variation in primary carnitine deficiency. Genetics in Medicine, 3(6), 387-392.

Phenotype and genotype variation in primary carnitine deficiency. / Wang, Yuhuan; Korman, Stanley H.; Ye, Jing; Gargus, J. Jay; Gutman, Alisa; Taroni, Franco; Garavaglia, Barbara; Longo, Nicola.

In: Genetics in Medicine, Vol. 3, No. 6, 2001, p. 387-392.

Research output: Contribution to journalArticle

Wang, Y, Korman, SH, Ye, J, Gargus, JJ, Gutman, A, Taroni, F, Garavaglia, B & Longo, N 2001, 'Phenotype and genotype variation in primary carnitine deficiency', Genetics in Medicine, vol. 3, no. 6, pp. 387-392.
Wang Y, Korman SH, Ye J, Gargus JJ, Gutman A, Taroni F et al. Phenotype and genotype variation in primary carnitine deficiency. Genetics in Medicine. 2001;3(6):387-392.
Wang, Yuhuan ; Korman, Stanley H. ; Ye, Jing ; Gargus, J. Jay ; Gutman, Alisa ; Taroni, Franco ; Garavaglia, Barbara ; Longo, Nicola. / Phenotype and genotype variation in primary carnitine deficiency. In: Genetics in Medicine. 2001 ; Vol. 3, No. 6. pp. 387-392.
@article{f3aa8e3a294b43ccb0faa7aa94bca25c,
title = "Phenotype and genotype variation in primary carnitine deficiency",
abstract = "Purpose: 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.",
keywords = "Cardiomyopathy, Carnitine deficiency, Developmental delay, Fatty acid oxidation, OCTN2",
author = "Yuhuan Wang and Korman, {Stanley H.} and Jing Ye and Gargus, {J. Jay} and Alisa Gutman and Franco Taroni and Barbara Garavaglia and Nicola Longo",
year = "2001",
language = "English",
volume = "3",
pages = "387--392",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Phenotype and genotype variation in primary carnitine deficiency

AU - Wang, Yuhuan

AU - Korman, Stanley H.

AU - Ye, Jing

AU - Gargus, J. Jay

AU - Gutman, Alisa

AU - Taroni, Franco

AU - Garavaglia, Barbara

AU - Longo, Nicola

PY - 2001

Y1 - 2001

N2 - Purpose: 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.

AB - Purpose: 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.

KW - Cardiomyopathy

KW - Carnitine deficiency

KW - Developmental delay

KW - Fatty acid oxidation

KW - OCTN2

UR - http://www.scopus.com/inward/record.url?scp=0035746511&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035746511&partnerID=8YFLogxK

M3 - Article

VL - 3

SP - 387

EP - 392

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 6

ER -