Identification of 12 novel mutations in the SLC3A1 gene in Swedish cystinuria patients

Cystinuria is an autosomal recessive disorder that affects luminal transpor t of cystine and dibasic amino acids in the kidneys and the small intestine . Three subtypes of cystinuria can be defined biochemically, and the classi cal form (type I) has been associated with mutations in the amino acid tran sporter gene SLC3A1. The mutations detected in SLC3A1 tend to be population specific and have not been previously investigated in Sweden. We have scre ened the entire coding sequence and the intron/exon boundaries of the SLC3A 1 gene in 53 cystinuria patients by means of single strand conformation pol ymorphism (SSCP) and DNA sequencing. We identified 12 novel mutations (a 2 bp deletion, one splice site mutation, and 10 missense mutations) and detec ted another three mutations that were previously reported. Five polymorphis ms were also identified, four of which were formerly described. The most fr equent mutation in this study was the previously reported M467T and it was also detected in the normal population with an allelic frequency of 0.5%. T hirty,seven patients were homozygous for mutations in the SLC3A1 gene and a nother seven were heterozygous which implies that other genes may be involv ed in cystinuria. Future investigation of the non-type I cystinuria gene SL C7A9 may complement our results but recent studies also suggest the presenc e of other potential disease genes. Hum Mutat 18:516-525, 2001. (C) 2001 Wi ley-Liss, Inc.