MOLECULAR ANALYSIS OF THE CYSTINURIA DISEASE GENE - IDENTIFICATION OF4 NEW MUTATIONS, ONE LARGE DELETION, AND ONE POLYMORPHISM

A cystinuria disease gene (rBAT) has recently been identified, but evi dence strongly suggests that only Type-I cystinuria is due to mutation s in this gene. Sixteen point mutations and a large deletion causing t he disease have so far been described in the rBAT gene sequence. To id entify new mutated alleles, genomic DNA was analyzed, after the determ ination of the entire genomic structure of the rBAT gene, by RNA-singl e strand conformation polymorphism analysis, an accurate and sensitive method able to detect nucleotide changes. Four new point mutations, a large deletion, and a common intragenic polymorphism were detected. T hese new mutations increase to 22 the number of mutated alleles so far characterized in rBAT. In addition, the frequency of 21 mutations was assessed in a sample of accurately defined Type-I cystinuria choromos omes. They account for about 58% of all Type-I chromosomes, mutation M 467T being the most common (0.26).