Copyright © 2000 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 66, Issue 1, 92-99, 1 January 2000
doi:10.1086/302700
Structure of the SLC7A7 Gene and Mutational Analysis of Patients Affected by Lysinuric Protein Intolerance
Maria Pia Sperandeo1, *, Maria Teresa Bassi2, *, Mirko Riboni2, Giancarlo Parenti1, Anna Buoninconti1, Marta Manzoni2, Barbara Incerti2, Maria Rosaria Larocca1, Maja Di Rocco5, Pietro Strisciuglio6, Irma Dianzani7, Rossella Parini3, Miranda Candito8, Fumio Endo9, Andrea Ballabio2, 4, Generoso Andria1, Gianfranco Sebastio1, 
, 
and Giuseppe Borsani2, ,
1 Department of Pediatrics, Federico II University, Naples
2 Telethon Institute of Genetics and Medicine (TIGEM) San Raffaele Biomedical Science Park, Milan
3 Clinica Pediatrica II, Istituti Clinici di Perfezionamento, Milan
4 Università Vita e Salute, San Raffaele, Milan
5 II Divisione di Pediatria, Istituto G. Gaslini, Genoa
6 Department of Pediatrics, University of Reggio Calabria, Catanzaro
7 Dipartimento di Scienze Mediche, Università del Piemonte Orientale “A. Avogadro,” Novara, Italy
8 Laboratoire de Biochimie, Hôpital Pasteur, Nice, France
9 Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto, Japan
Addresses for correspondence and reprints: Dr. Gianfranco Sebastio, Department of Pediatrics, Federico II University, Via Sergio Pansini 5, 80131 Naples, ItalyDr. Giuseppe Borsani, Telethon Institute of Genetics and Medicine (TIGEM), San Raffaele Biomedical Science Park, Via Olgettina 58, 20132 Milan, Italy* These two authors contributed equally to this work.
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.
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