PMID- 10080182
OWN - NLM
STAT- MEDLINE
DCOM- 19990331
LR  - 20131121
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 21
IP  - 3
DP  - 1999 Mar
TI  - Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance 
      gene.
PG  - 293-6
AB  - Lysinuric protein intolerance (LPI; OMIM 222700) is a rare, recessive disorder
      with a worldwide distribution, but with a high prevalence in the Finnish
      population; symptoms include failure to thrive, growth retardation, muscle
      hypotonia and hepatosplenomegaly. A defect in the plasma membrane transport of
      dibasic amino acids has been demonstrated at the baso-lateral membrane of
      epithelial cells in small intestine and in renal tubules and in plasma membrane
      of cultured skin fibroblasts from LPI patients. The gene causing LPI has been
      assigned by linkage analysis to 14q11-13. Here we report mutations in SLC7A7 cDNA
      (encoding y+L amino acid transporter-1, y+LAT-1), which expresses dibasic
      amino-acid transport activity and is located in the LPI region, in 31 Finnish LPI
      patients and 1 Spanish patient. The Finnish patients are homozygous for a founder
      missense mutation leading to a premature stop codon. The Spanish patient is a
      compound heterozygote with a missense mutation in one allele and a frameshift
      mutation in the other. The frameshift mutation generates a premature stop codon, 
      eliminating the last one-third of the protein. The missense mutation abolishes
      y+LAT-1 amino-acid transport activity when co-expressed with the heavy chain of
      the cell-surface antigen 4F2 (4F2hc, also known as CD98) in Xenopus laevis
      oocytes. Our data establish that mutations in SLC7A7 cause LPI.
FAU - Torrents, D
AU  - Torrents D
AD  - Departament de Bioquimica i Biologia Molecular, Universitat de Barcelona, Spain.
FAU - Mykkanen, J
AU  - Mykkanen J
FAU - Pineda, M
AU  - Pineda M
FAU - Feliubadalo, L
AU  - Feliubadalo L
FAU - Estevez, R
AU  - Estevez R
FAU - de Cid, R
AU  - de Cid R
FAU - Sanjurjo, P
AU  - Sanjurjo P
FAU - Zorzano, A
AU  - Zorzano A
FAU - Nunes, V
AU  - Nunes V
FAU - Huoponen, K
AU  - Huoponen K
FAU - Reinikainen, A
AU  - Reinikainen A
FAU - Simell, O
AU  - Simell O
FAU - Savontaus, M L
AU  - Savontaus ML
FAU - Aula, P
AU  - Aula P
FAU - Palacin, M
AU  - Palacin M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Amino Acid Transport Systems, Basic)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 3.1.21.- (endodeoxyribonuclease DdeI)
RN  - EC 3.1.21.4 (Deoxyribonucleases, Type II Site-Specific)
RN  - GMW67QNF9C (Leucine)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Adolescent
MH  - Amino Acid Metabolism, Inborn Errors/*genetics
MH  - Amino Acid Sequence
MH  - Amino Acid Transport Systems, Basic
MH  - Animals
MH  - Arginine/metabolism
MH  - Biological Transport
MH  - Carrier Proteins/*genetics/metabolism
MH  - Deoxyribonucleases, Type II Site-Specific/genetics
MH  - Female
MH  - Finland
MH  - Heterozygote
MH  - Humans
MH  - Introns
MH  - Leucine/metabolism
MH  - Lysine/urine
MH  - Male
MH  - Membrane Proteins/*genetics/metabolism
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Oocytes/physiology
MH  - *Sequence Deletion
MH  - Xenopus
EDAT- 1999/03/18 03:02
MHDA- 2001/03/23 10:01
CRDT- 1999/03/18 03:02
PHST- 1999/03/18 03:02 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/03/18 03:02 [entrez]
AID - 10.1038/6809 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Mar;21(3):293-6. doi: 10.1038/6809.