Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder |
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Authors: | Kleta Robert Romeo Elisa Ristic Zorica Ohura Toshihiro Stuart Caroline Arcos-Burgos Mauricio Dave Mital H Wagner Carsten A Camargo Simone R M Inoue Sumiko Matsuura Norio Helip-Wooley Amanda Bockenhauer Detlef Warth Richard Bernardini Isa Visser Gepke Eggermann Thomas Lee Philip Chairoungdua Arthit Jutabha Promsuk Babu Ellappan Nilwarangkoon Sirinun Anzai Naohiko Kanai Yoshikatsu Verrey Francois Gahl William A Koizumi Akio |
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Institution: | 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. |
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Abstract: | 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. |
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