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 patient 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 mutation was located and is a single nucleotide deletion at position 570/571 of the DHPR cDNA sequence and results in a frameshift and premature termination after the addition of six amino acids. The mutation is present in a homozygous state in the patient and in a heterozygous state 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, and confirms our observation that exon 4 skipping is a relatively common event.