Mutations in the SLC3A1 gene and the molecular basis of cystinuria
- and others
Cystinuria is an autosomal recessive disease characterized by excessive urinary excretion of cystine and the dibasic amino acids. The major clinical manifestation of the disease is the development of kidney stones due to the poor solubility of cystine in the urine. Approximately 1:60 Americans is a heterozygote for cystinuria; among Libyan Jews the carrier frequency is 1:25. Three types of carriers have been described based on urinary cystine levels in heterozygotes. We recently mapped the disease susceptibility locus to chromosome 2p in a panel of 17 Israeli and American families, without evidence for locus heterogeneity. Another group simultaneously identified six cystinuria-associated missense mutations in the SLC3A1 (rBAT, D2H) gene, which is found on chromosome 2. This gene encodes a protein in the renal tubular epithelium that resorbs filtered cystine from the urine. Here we report two additional SLC3A1 mutations associated with cystinuria in an American family. In one parent we found a single base insertion at position 1306, causing a frame shift and downstream premature stop codon, while in the other parent we found a deletion spanning at least the first half of the cDNA. Despite the fact that the parents had significantly altered or no messenger RNA from one allele, both exhibited normal urinary cystine levels. This observation suggests that in those heterozygotes who have increased urinary cystine levels, the mutant protein may interfere with the function of the normal SLC3A1 gene product. None of the eight known mutations were found in 16 other cystinuria families that we have screened, suggesting that many more mutations exist. We are currently screening these families for new mutations.
- OSTI ID:
- 134288
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1021
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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