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Mutations in the SLC3A1and SLC7A9genes cause cystinuria (OMIM 220100), an autosomal recessive disorder of amino acid transport and reabsorption in the proximal renal tubule and in the epithelial cells of the gastrointestinal tract. In an attempt to characterize the molecular defect in the SLC3A1and SLC7A9genes, we analyzed a cohort of 85 unrelated subjects clinically diagnosed as affected by cystinuria on the basis of stone formation, prevalently of Italian and Greek origin. Analysis of all coding region and exon–intron junctions of the SLC3A1and SLC7A9genes by using direct sequencing method allowed us to identify 62 different mutations in 83 out of 85 patients accounting for 90.5 of all affected chromosomes. Twenty-four out of 62 are novel mutations, 9 in SLC3A1and 15 in SLC7A9. In conclusion, this report expands the spectrum of SLC3A1and SLC7A9mutations and confirms the heterogeneity of this disorder. [ABSTRACT FROM AUTHOR]

Purpose: To identify the genetic defect associated with keratoconus (KC) in an Ashkenazi Jewish family and to evaluate its nature and its phenotypic expression within carriers. Methods: A three generation Ashkenazi Jewish family with KC was ascertained. Diagnosis was based on clinical examination and corneal topography. Segregation analysis was performed using micro-satellite polymorphic markers in close proximity to 7 previously associated KC loci and genes. Mutation analysis of the VSX1 gene was performed by direct sequencing of PCR-amplified exons, and a BseR1 restriction assay. In selected cases, where the genotype was consistent with KC, additional effort to detect subtle corneal changes was made by computerized Orbscan measurements. Results: We found co-segregation between the KC phenotype and a polymorphic marker close to the VSX1. Sequencing revealed a previously described missense mutation (D144E). All of the mutation carriers manifested pathologic corneal findings; some had overt KC while others had subtle corneal alterations identifiable only by Orbscan. Conclusions: These findings support the pathogenic role of VSX1 gene in KC. The variable expression among the carriers, suggests the involvement of other factors in determining the final phenotype. [ABSTRACT FROM AUTHOR]