title: Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat.
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.
authors: Medical and Molecular Genetics Center, IDIBELL, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain. mfont@idibell.org
authors: Mariona
authors: M
authors: Font-Llitjós
authors: Benjamín
authors: B
authors: Rodríguez-Santiago
authors: Meritxell
authors: M
authors: Espino
authors: Ruth
authors: R
authors: Sillué
authors: Sandra
authors: S
authors: Mañas
authors: Laia
authors: L
authors: Gómez
authors: Luis A
authors: LA
authors: Pérez-Jurado
authors: Manuel
authors: M
authors: Palacín
authors: Virginia
authors: V
authors: Nunes
mesh_terms: D000293:Adolescent; D020087:Alu Elements; D000595:Amino Acid Sequence; D020157:Amino Acid Transport Disorders, Inborn / Q000235:genetics*; D027241:Amino Acid Transport System y+L; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D027301:Fusion Regulatory Protein 1, Light Chains / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D007438:Introns; D008239:Lysine / Q000652:urine*; D008297:Male; D017354:Point Mutation
chemical_list: D027241:Amino Acid Transport System y+L; D027301:Fusion Regulatory Protein 1, Light Chains; C421261:SLC7A7 protein, human; D008239:Lysine