title: Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance.
abstract: Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of cationic amino acid transport caused by mutations in the SLC7A7 gene. We report the genomic structure of the gene and the results of the mutational analysis in Italian, Tunisian, and Japanese patients. The SLC7A7 gene consists of 10 exons; sequences of all of the exon-intron boundaries are reported here. All of the mutant alleles were characterized and eight novel mutations were detected, including two missense mutations, 242A-->C (M1L) and 1399C-->A (S386R); a nonsense mutation 967G-->A (W242X); two splice mutations IVS3 +1G-->A and IVS6 +1G-->T; a single-base insertion, 786insT; and two 4-bp deletions, 455delCTCT and 1425delTTCT. In addition, a previously reported mutation, 1625insATCA, was found in one patient. It is noteworthy that 242A-->C causes the change of Met1 to Leu, a rare mutational event previously found in a few inherited conditions. We failed to establish a genotype/phenotype correlation. In fact, both intrafamilial and interfamilial phenotypic variability were observed in homozygotes for the same mutation. The DNA-based tests are now easily accessible for molecular diagnosis, genetic counseling, and prenatal diagnosis of LPI.
authors.affiliation: Department of Pediatrics, Federico II University, Naples.
authors.forename: M P
authors.initials: MP
authors.lastname: Sperandeo
authors.forename: M T
authors.initials: MT
authors.lastname: Bassi
authors.forename: M
authors.initials: M
authors.lastname: Riboni
authors.forename: G
authors.initials: G
authors.lastname: Parenti
authors.forename: A
authors.initials: A
authors.lastname: Buoninconti
authors.forename: M
authors.initials: M
authors.lastname: Manzoni
authors.forename: B
authors.initials: B
authors.lastname: Incerti
authors.forename: M R
authors.initials: MR
authors.lastname: Larocca
authors.forename: M
authors.initials: M
authors.lastname: Di Rocco
authors.forename: P
authors.initials: P
authors.lastname: Strisciuglio
authors.forename: I
authors.initials: I
authors.lastname: Dianzani
authors.forename: R
authors.initials: R
authors.lastname: Parini
authors.forename: M
authors.initials: M
authors.lastname: Candito
authors.forename: F
authors.initials: F
authors.lastname: Endo
authors.forename: A
authors.initials: A
authors.lastname: Ballabio
authors.forename: G
authors.initials: G
authors.lastname: Andria
authors.forename: G
authors.initials: G
authors.lastname: Sebastio
authors.forename: G
authors.initials: G
authors.lastname: Borsani
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D007558:Italy; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D014416:Tunisia
chemical_list: D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008565:Membrane Proteins