Molecular Genetics of Cystinuria


Among the kidney stone diseases, cystinuria (OMIM 220100) is unique as it is exclusively caused by genomic alterations. Cystinuria is associated with mutations in the SLC3A1 and the SLC7A9 genes encoding the subunits rBAT and b0,+AT of the renal b0,+ transporter. Mutations in SLC3A1 are usually inherited autosomal recessively, but SLC7A9 mutations result in a broad clinical variability. The detection rate for mutations is influenced by the ethnic origin of the patient and by the functional significance of the variant. As a result, mutations cannot be detected in 100% of alleles, but it reaches approximately 85%. In case of SLC3A1, large rearrangements in 2p21 cause cystinuria and severe hypotonia (hypotonia–cystinuria syndrome – HCS). Meanwhile, a large number of mutations in both genes have been reported, several of these variants were functionally analysed. Thereby, the aetiology of the disease as well as the physiological mechanisms of the renal trafficking of cystine could be deciphered.

Key Concepts:

  • Cystinuria is characterised by the defect transport of cystine, resulting in cystine stone formation.

  • With SLC3A1 and SLC7A9, two disease causing genes have been identified.

  • SLC3A1 and SLC7A9 encode the two subunits of the amino acid transporter b0,+.

  • Mutations in SLC3A1 are predominantly associated with an autosomal recessive inheritance, whereas SLC7A9 mutations show an autosomal dominant inheritance with an incomplete penetrance.

  • Homozygosity for large genomic deletions affecting both the SLC3A1 and the PREPL gene in 2p21 cause the hypotonia–cystinuria syndrome.

Keywords: cystinuria; molecular Genetics; SLC3A1; SLC7A9; mutations; hypotonia‐cystinuria syndrome

Figure 1.

Cellular localisation and function of rBAT (SLC3A1) and b0,+AT (SLC7A9). (amino acids, AA).



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Further Reading

Eggermann T, Venghaus A and Zerres K (2012) Cystinuria: an inborn cause of urolithiasis. Orphanet Journal of Rare Diseases 7: 19.

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Eggermann, Thomas(Oct 2012) Molecular Genetics of Cystinuria. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0024440]