I. Dianzani

Phenotype characterization and prevalence of rBAT M467T mutation in Italian cystinuric patients

Cystinuria (McKusick 220100) is an inherited disorder affecting the transport of cystine (Cys) and dibasic amino acids arginine (Arg), lysine (Lys) and ornithine (Orn) in the epithelial cells of both jejunum and proximal convoluted tubule, with an overall prevalence of 1 :7000. The only relevant consequence at clinical level is the urolithiasis due to the low solubility of Cys and the complications caused by renal stone disease. The occurrence of at least three distinct clinical types of cystinuria raises the question whether cystinuria is a single disease or a group of different conditions with impaired amino acid transport. Recently, a gene encoding a Cys and dibasic amino acid transporter (rBAT) has been identified (Bertran et al 1993) and several mutations in this gene have been found in cystinuric patients (Gasparini et al 1995). One mutation, M467T, was found to be prevalent in the Spanish population (40%) (Calonge et al 1994). The aim of this study was to analyse the phenotype distribution and the prevalence of rBAT M467T mutation in Italian cystinuric patients.

Molecular Basis of Phenylketonuria in Italy

In recent years, a lot of data have been produced to elucidate the molecular basis of phenylketonuria (PKU), the disease caused by the deficiency of the liver enzyme phenylalanine hydroxylase (PAH). The identification of the RFLP haplotypes associated to the PAH gene has offered the means for prenatal diagnosis and carrier detection, previously infeasible or not always reliable by using biochemical methods. The characterization of the causal mutations may extend both these analyses, available only for selected families by RFLP studies, to the entire population. So far more than thirty mutations have been identified (ref. in 1 7). Most of the studies have been focussed on North European populations and for many of them 50 to 70% of the PKU causal mutations have been identified. On the other hand, the information about Mediterranean populations is scanty.