A MUTATION CAUSING DHPR DEFICIENCY RESULTS IN A FRAMESHIFT AND A SECONDARY SPLICING DEFECT

In our analysis of mutations causing DHPR deficiency we identified a p atient in whom there was an aberrant transcription pattern detected by PCR of DHPR cDNA. However, unlike the pattern observed as a result of most splicing mutations, there is some full length transcript. The mu tation was located and is a single nucleotide deletion at position 570 /571 of the DHPR cDNA sequence and results in a frameshift and prematu re termination after the addition of six amino acids. The mutation is present in a homozygous state in the patient and in a heterozygous sta te in both parents. The exon which is deleted at high frequency in the patient is the putative exon 4, which is remote from the mutation, an d confirms our observation that exon 4 skipping is a relatively common event.