TY - JOUR
T1 - Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance
AU - Sperandeo, Maria Pia
AU - Bassi, Maria Teresa
AU - Riboni, Mirko
AU - Parenti, Giancarlo
AU - Buoninconti, Anna
AU - Manzoni, Marta
AU - Incerti, Barbara
AU - Larocca, Maria Rosaria
AU - Di Rocco, Maja
AU - Strisciuglio, Pietro
AU - Dianzani, Irma
AU - Parini, Rossella
AU - Candito, Miranda
AU - Endo, Fumio
AU - Ballabio, Andrea
AU - Andria, Generoso
AU - Sebastio, Gianfranco
AU - Borsani, Giuseppe
N1 - Funding Information:
We thank the families, for contributing to this project, and A. Pepe and M. R. Tuzzi, for technical assistance. We also thank the YAC Screening Center at San Raffaele Biomedical Science Park. Telethon Grant E.652 is gratefully acknowledged. This work was supported by MURST Cofin 1998 (to G.S.).
PY - 2000
Y1 - 2000
N2 - 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 Met 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.
AB - 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 Met 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.
UR - http://www.scopus.com/inward/record.url?scp=0033909657&partnerID=8YFLogxK
U2 - 10.1086/302700
DO - 10.1086/302700
M3 - Article
SN - 0002-9297
VL - 66
SP - 92
EP - 99
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -