Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19.
Hartnup disorder (OMIM 234500) is an autosomal recessive abnormality of renal and gastrointestinal neutral amino acid transport noted for its clinical variability. We localized a gene causing Hartnup disorder to chromosome 5p15.33 and cloned a new gene, SLC6A19, in this region. SLC6A19 is a sodium-dependent and chloride-independent neutral amino acid transporter, expressed predominately in kidney and intestine, with properties of system B(0). We identified six mutations in SLC6A19 that cosegregated with disease in the predicted recessive manner, with most affected individuals being compound heterozygotes. The disease-causing mutations that we tested reduced neutral amino acid transport function in vitro. Population frequencies for the most common mutated SLC6A19 alleles are 0.007 for 517G --> A and 0.001 for 718C --> T. Our findings indicate that SLC6A19 is the long-sought gene that is mutated in Hartnup disorder; its identification provides the opportunity to examine the inconsistent multisystemic features of this disorder.
Seow
Heng F
HF
Gene Therapy, Centenary Institute of Cancer Medicine & Cell Biology, University of Sydney, NSW 2042, Australia.
Bröer
Stefan
S
Bröer
Angelika
A
Bailey
Charles G
CG
Potter
Simon J
SJ
Cavanaugh
Juleen A
JA
Rasko
John E J
JE
D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5; D003001:Cloning, Molecular; D005787:Gene Frequency; D006250:Hartnup Disease / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
D026921:Amino Acid Transport Systems, Neutral; C491436:SLC6A19 protein, human