The molecular basis of cystinuria: An update

Cystinuria is a hereditary disorder of cystine and dibasic amino acid trans port across the luminal membrane of renal proximal tubule and small intesti ne. In 1992, a cDNA (rBAT) was isolated from kidney which induced high-affi nity, sodium-independent uptake of cystine and dibasic amino acids when exp ressed in Xenopus oocytes, The rBAT gene was mapped to a region of chromoso me 2p known to contain a cystinuria locus, and rBAT expression was demonstr ated in the straight (S3) portion of renal proximal tubule and small intest ine. Over 30 distinct rBAT mutations have been described in patients who in herit two fully recessive (type I) cystinuria genes. Recently, the second c ystinuria gene (SLC7A9) on chromosome 19q was identified; SLC7A9 mutations were shown to cause the incompletely recessive form of cystinuria (types II and Ill), Patients who inherit two mutant SLC7A9 genes have recurrent neph rolithiasis comparable to those with two rBAT mutations. In some cystinuria families, patients inherit a fully recessive allele from one parent and an incompletely recessive allele from the other parent; patients with this 'm ixed type' of cystinuria have somewhat milder disease. It is not yet clear whether this form of cystinuria involves rBAT as well as SLC7A9 mutations. Current evidence suggests that the transmembrane channel mediating uptake o f cystine and dibasic amino acids at the luminal surface is encoded by SLC7 A9; the smaller rBAT protein forms a heterodimeric complex with this channe l and is critical for its targetting to the luminal membrane. Copyright (C) 2000 S. KargerAG, Basel.