Background: Cystinuria is an autosomal recessive disease that is manifested by kidney stones and is caused by mutations in two genes: SLC3A1 on chromosome 2p and SLC7A9 on chromosome 19q. Urinary cystine levels in obligate carriers are often, but not always, helpful in identifying the causative gene.
Objectives: To characterize the clinical features and analyze the genetic basis of cystinuria in an inbred Moslem Arab Israeli family.
Methods: Family members were evaluated for urinary cystine and amino acid levels. DNA was initially analyzed with polymorphic markers close to the two genes and SLC7A9 was fully sequenced.
Results: Full segregation was found with the marker close to SLC7A9. Sequencing of this gene revealed a missense mutation, P482L, in the homozygous state in all three affected sibs.
Conclusions: A combination of urinary cystine levels in obligate carriers, segregation analysis with polymorphic markers, and sequencing can save time and resources in the search for cystinuria mutations.