A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency.

摘要: Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterized by thymine-uraciluria and associated with a variable clinical phenotype. In order to identify the molecular defect underlying complete DPD in Dutch patient previously shown have 165 base pair deletion mature mRNA, we cloned genomic region encompassing skipped exon its flanking intron sequences. Sequence analysis revealed that was homozygous for single G→A point mutation invariant GT dinucleotide splice donor site downstream of exon. The same identified another, unrelated, patient. Because this destroys uniqueMaeII restriction site, rapid screening using enzyme cleavage amplified possible. Analysis 50 controls no individuals heterozygous