Molecular characterization of Turkish patients with pyrimidine 5′ nucleotidase-I deficiency

Pyrimidine 5' nucleotidase-I (P5N-I) deficiency is a rare autosomal recessive disorder associated with hemolytic anemia, marked basophilic stippling, and accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. Recently, the structure and location of the P5N-I gene have been published. This paper presents the results of a study characterizing the molecular pathologies of P5N-I deficiency in a total of 6 Turkish patients from 4 unrelated families of consanguineous marriages. Mutation analysis in the P5N-I gene led to the identification of 3 novel mutations in these patients. In 4 patients from 2 families, a homozygous insertion of double G at position 743 was detected in exon 9 (743-744insGG), leading to premature termination of translation 23 bp downstream. In one family, a homozygous T to G transition at position 543 (543T>G) in exon 8 resulted in the replacement of tyrosine (Tyr) with a stop codon (Tyr181Stop). In another family, a homozygous insertion of a single A in exon 7 (384-385insA) created a stop signal at the codon nearby. In all families, the parents were heterozygous for the relevant mutations. None of these changes was detected in 200 chromosomes from a healthy Turkish population. These mutations were not correlated with any particular phenotype.