Document Detail

Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat.
MedLine Citation:
PMID:  18716612     Owner:  NLM     Status:  MEDLINE    
Lysinuric protein intolerance (LPI) is a rare autosomal inherited disease caused by defective cationic aminoacid transport 4F2hc/y(+)LAT-1 at the basolateral membrane of epithelial cells in the intestine and kidney. LPI is a multisystemic disease with a variety of clinical symptoms such as hepatosplenomegaly, osteoporosis, hypotonia, developmental delay, pulmonary insufficiency or end-stage renal disease. The SLC7A7 gene, which encodes the y(+)LAT-1 protein, is mutated in LPI patients. Mutation analysis of the promoter localized in intron 1 and all exons of the SLC7A7 gene was performed in 11 patients from 9 unrelated LPI families. Point mutation screening was performed by exon direct sequencing and a new multiplex ligation probe amplification (MLPA) assay was set up for large rearrangement analysis. Eleven SLC7A7-specific mutations were identified, seven of them were novel: p.L124P, p.C425R, p.R468X, p.Y274fsX21, c.625+1G>C, DelE4-E11 and DelE6-E11. The novel large deletions originated by the recombination of Alu repeats at introns 3 and 5, respectively, with the same AluY sequence localized at the SLC7A7 3' region. The novel MLPA assay is robust and valuable for LPI molecular diagnosis. Our results suggest that genomic rearrangements of SLC7A7 play a more important role in LPI than has been reported, increasing the detection rate from 5.1 to 21.4%. Moreover, the 3' region AluY repeat could be a recombination hot spot as it is involved in 38% of all SLC7A7 rearranged chromosomes described so far.
Mariona Font-Llitjós; Benjamín Rodríguez-Santiago; Meritxell Espino; Ruth Sillué; Sandra Mañas; Laia Gómez; Luis A Pérez-Jurado; Manuel Palacín; Virginia Nunes
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-20
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  17     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-02-05     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  71-9     Citation Subset:  IM    
Medical and Molecular Genetics Center, IDIBELL, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain.
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MeSH Terms
Alu Elements*
Amino Acid Sequence
Amino Acid Transport Disorders, Inborn / genetics*
Antigens, CD98 Light Chains / genetics*
Child, Preschool
DNA Mutational Analysis
Gene Rearrangement
Lysine / urine*
Point Mutation
Reg. No./Substance:
0/Antigens, CD98 Light Chains; 0/SLC7A7 protein, human; 56-87-1/Lysine

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