Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder.
Hartnup disorder, an autosomal recessive defect named after an English family described in 1956 (ref. 1), results from impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa. Symptoms include transient manifestations of pellagra (rashes), cerebellar ataxia and psychosis. Using homozygosity mapping in the original family in whom Hartnup disorder was discovered, we confirmed that the critical region for one causative gene was located on chromosome 5p15 (ref. 3). This region is homologous to the area of mouse chromosome 13 that encodes the sodium-dependent amino acid transporter B(0)AT1 (ref. 4). We isolated the human homolog of B(0)AT1, called SLC6A19, and determined its size and molecular organization. We then identified mutations in SLC6A19 in members of the original family in whom Hartnup disorder was discovered and of three Japanese families. The protein product of SLC6A19, the Hartnup transporter, is expressed primarily in intestine and renal proximal tubule and functions as a neutral amino acid transporter.
Medical Genetics Branch, 10 Center Drive, MSC 1851, Building 10, Room 10C-107, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Robert
R
Kleta
Elisa
E
Romeo
Zorica
Z
Ristic
Toshihiro
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Ohura
Caroline
C
Stuart
Mauricio
M
Arcos-Burgos
Mital H
MH
Dave
Carsten A
CA
Wagner
Simone R M
SR
Camargo
Sumiko
S
Inoue
Norio
N
Matsuura
Amanda
A
Helip-Wooley
Detlef
D
Bockenhauer
Richard
R
Warth
Isa
I
Bernardini
Gepke
G
Visser
Thomas
T
Eggermann
Philip
P
Lee
Arthit
A
Chairoungdua
Promsuk
P
Jutabha
Ellappan
E
Babu
Sirinun
S
Nilwarangkoon
Naohiko
N
Anzai
Yoshikatsu
Y
Kanai
Francois
F
Verrey
William A
WA
Gahl
Akio
A
Koizumi
D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D006250:Hartnup Disease / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
D026921:Amino Acid Transport Systems, Neutral; C491436:SLC6A19 protein, human