Genetic Heterogeneity in Cystinuria: The SLC3A1 Gene is Linked to Type I but not to Type III Cystinuria

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 21; pp. 9667 - 9671
• Main Authors: Calonge, Maria Julia, Volpini, Victor, Bisceglia, Luigi, Rousaud, Ferran, de Sanctis, Luisa, Beccia, Ercole, Zelante, Leopoldo, testar, Xavier, Zorzano, Antonio, Estivill, Xavier, Gasparini, Paolo, Nunes, Virginia, Palacini, Manuel
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 10.10.1995; National Acad Sciences; National Academy of Sciences
• Subjects: Adolescent; Adult; Amino Acid Transport Systems, Basic; amino acid transporter; Amino acids; Amino Acids, Diamino - urine; aminoaciduria; Belgium; Carrier Proteins - genetics; Child; Chromosomes, Human, Pair 2 - genetics; Creatinine - urine; Cystinuria; Cystinuria - classification; Cystinuria - diagnosis; Cystinuria - genetics; Diamino amino acids; Excretion; Female; Genes; Genetic Heterogeneity; Genetic loci; Genetic Markers; Genetic mutation; Genetics; Genotype; Heterozygotes; Humans; Italy; linkage analysis; Lod Score; Male; man; Medical disorders; Medical genetics; Membrane Glycoproteins - genetics; Middle Aged; Mutation; Pedigree; Phenotypes; rBAT gene; SCL3A1 gene; Spain; Belgium; Italy; Spain
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.21.9667

Cystinuria is an autosomal recessive aminoaciduria where three urinary phenotypes have been described (I, II, and III). An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. To assess whether mutations in SLC3A1 are involved in different cystinuria phenotypes, linkage with this gene and its nearest marker (D2S119) was analyzed in 22 families with type I and/or type III cystinuria. Linkage with heterogeneity was proved (α = 0.45; P < 0.008). Type I/I families showed homogeneous linkage to SLC3A1 (Zmax> 3.0 at θ = 0.00; α = 1), whereas types I/III and III/III were not linked. Our data suggest that type I cystinuria is due to mutations in the SLC3A1 gene, whereas another locus is responsible for type III. This result establishes genetic heterogeneity for cystinuria, classically considered as a multiallelic monogenic disease.