The molecular basis of Dutch infantile nephropathic cystinosis

Infantile nephropathic cystinosis, an inborn error of metabolism with an au tosomal recessive inheritance pattern, is characterized by lysosomal storag e of the amino acid cystine due to an impaired transport of cystine out of the lysosomes. Initial clinical features consist of the renal Fanconi syndr ome and crystals in the cornea. Oral therapy with cysteamine lowers the int racellular cystine content. Recently, the gene coding for the integral memb rane protein cystinosin, which is responsible for membrane transport of cys tine (CTNS), was cloned. Mutation analysis of the CTNS gene of Caucasian pa tients revealed a common 57-kb deletion, and several other mutations spread throughout the entire gene. In the present study, we developed an improved screening method for the detection of the common 57-kb deletion. By use of this method we detected the 57-kb deletion in 59% of the examined Dutch al leles. The remaining alleles were screened for other mutations by genomic s equencing of the different exons, revealing three previously described muta tions. Furthermore, we studied a possible genotype-phenotype relation of th e homozygous deleted patients, which could not be demonstrated in our study population. Next to biochemical determination of cystine in leukocytes or fibroblasts, molecular genetic analysis enables prenatal diagnosis and faci litates identification of carriers. Copyright (C) 2001 S. Karger AG, Basel.