Journal of Inherited Metabolic Disease

, Volume 25, Issue 6, pp 437–448

Hartnup disorder: Polymorphisms identified in the neutral amino acid transporter SLC1A5

Authors

  • S. J. Potter
    • Centenary Institute of Cancer Medicine and Cell Biology
  • A. Lu
    • Centenary Institute of Cancer Medicine and Cell Biology
  • B. Wilcken
    • New South Wales Biochemical Genetics ServiceThe Children's Hospital at Westmead
  • K. Green
    • New South Wales Biochemical Genetics ServiceThe Children's Hospital at Westmead
    • Centenary Institute of Cancer Medicine and Cell Biology
    • Sydney Cancer CentreRoyal Prince Alfred Hospital
    • Gene Therapy Research UnitCentenary Institute
Article

DOI: 10.1023/A:1021286714582

Cite this article as:
Potter, S.J., Lu, A., Wilcken, B. et al. J Inherit Metab Dis (2002) 25: 437. doi:10.1023/A:1021286714582

Abstract

Hartnup disorder is an inborn error of renal and gastrointestinal neutral amino acid transport. The cloning and functional characterization of the 'system B0' neutral amino acid transporter SLC1A5 led to it being proposed as a candidate gene for Hartnup disorder. Linkage analysis performed at 19q13.3, the chromosomal position of SLC1A5, was suggestive of an association with the Hartnup phenotype in some families. However, SLC1A5 was not linked to the Hartnup phenotype in other families. Linkage analysis also excluded an alternative candidate region at 11q13 implicated by a putative mouse model for Hartnup disorder. Sequencing of the coding region of SLC1A5 in Hartnup patients revealed two coding region polymorphisms. These mutations did not alter the predicted amino acid sequence of SLC1A5 and were considered unlikely to play a role in Hartnup disorder. There were no mutations in splice sites flanking each exon. Quantitative RT-PCR of SLC1A5 messenger RNA in affected and unaffected subjects did not support systemic differences in expression as an explanation for Hartnup disorder. In the six unrelated Hartnup pedigrees studied, examination of linkage at 19q13.3, polymorphisms in the coding sequence and quantitation of expression of SLC1A5 did not suffice to explain the defect in neutral amino acid transport.

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© Kluwer Academic Publishers 2002