A NOVEL RNA SPLICING MUTATION IN JAPANESE PATIENTS WITH WILSON DISEASE

Deletion/insertion mutation of Wilson disease (WD) gene in 16 Japanese patients with Wilson disease was studied. A truncated size in a regio n of exon 4 to 6 was found by reverse transcription-polymerase chain r eaction (RT-PCR) covering entire 21 exons except exon 1 for liver cDNA of one patient with a late onset neurologic type. Sequence analysis o f the cDNA revealed that this truncation was occurred by skipping of e xon 5, though any mutation in exon 5 of genomic DNA was failed to dete ct. T to G transversion in 5 bp upstream from a junction of intron 4 a nd exon 5 was found in genomic DNA of the patient. Further, results ob tained by RT-PCR and the sequence analysis in intron 4 indicate that t he mutation of the patient is homozygous. Since same mutation in one a llele of another patient out of 15 patients was found, allele frequenc y of the splicing mutation in Japanese patients is 9.4%. These results suggest that the point mutation in intron 4 of WD gene causes the ski pping of exon 5 and the splicing mutation affects the phenotype of Wil son disease. (C) 1995 Academic Press, Inc.