Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat

Mariona Font-Llitjós, Benjamín Rodríguez-Santiago, Meritxell Espino Guarch, Ruth Sillué, Sandra Mañas, Laia Gómez, Luis A. Pérez-Jurado, Manuel Palacín, Virginia Nunes

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)71-79
Number of pages9
JournalEuropean Journal of Human Genetics
Volume17
Issue number1
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

Introns
Genetic Recombination
Ligation
Exons
Mutation
Muscle Hypotonia
Point Mutation
Genes
Osteoporosis
Chronic Kidney Failure
Intestines
Lysinuric Protein Intolerance
Chromosomes
Epithelial Cells
Kidney
Lung
Membranes
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat. / Font-Llitjós, Mariona; Rodríguez-Santiago, Benjamín; Espino Guarch, Meritxell; Sillué, Ruth; Mañas, Sandra; Gómez, Laia; Pérez-Jurado, Luis A.; Palacín, Manuel; Nunes, Virginia.

In: European Journal of Human Genetics, Vol. 17, No. 1, 2009, p. 71-79.

Research output: Contribution to journalArticle

Font-Llitjós, M, Rodríguez-Santiago, B, Espino Guarch, M, Sillué, R, Mañas, S, Gómez, L, Pérez-Jurado, LA, Palacín, M & Nunes, V 2009, 'Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat', European Journal of Human Genetics, vol. 17, no. 1, pp. 71-79. https://doi.org/10.1038/ejhg.2008.145
Font-Llitjós, Mariona ; Rodríguez-Santiago, Benjamín ; Espino Guarch, Meritxell ; Sillué, Ruth ; Mañas, Sandra ; Gómez, Laia ; Pérez-Jurado, Luis A. ; Palacín, Manuel ; Nunes, Virginia. / Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat. In: European Journal of Human Genetics. 2009 ; Vol. 17, No. 1. pp. 71-79.
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abstract = "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.",
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AU - Sillué, Ruth

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AU - Gómez, Laia

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