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.
Kleta
Robert
R
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.
Romeo
Elisa
E
Ristic
Zorica
Z
Ohura
Toshihiro
T
Stuart
Caroline
C
Arcos-Burgos
Mauricio
M
Dave
Mital H
MH
Wagner
Carsten A
CA
Camargo
Simone R M
SR
Inoue
Sumiko
S
Matsuura
Norio
N
Helip-Wooley
Amanda
A
Bockenhauer
Detlef
D
Warth
Richard
R
Bernardini
Isa
I
Visser
Gepke
G
Eggermann
Thomas
T
Lee
Philip
P
Chairoungdua
Arthit
A
Jutabha
Promsuk
P
Babu
Ellappan
E
Nilwarangkoon
Sirinun
S
Anzai
Naohiko
N
Kanai
Yoshikatsu
Y
Verrey
Francois
F
Gahl
William A
WA
Koizumi
Akio
A
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