A novel donor splice site mutation in the C1 inhibitor gene of a patient with type I hereditary angioneurotic edema

We studied the molecular genetic basis of a C1 inhibitor deficiency in a patient with type I hereditary angioneurotic edema using both the polymerase chain reaction and nucleotide sequencing. A single nucleotide change (T-->A) at the GT 5' donor splice recognition motif in the seventh intron of the C1 inhibitor gene was detected. A restriction site analysis of the C1 inhibitor gene in the patient's family indicated that this mutation is correlated with a decreased level of CI inhibitor activity. A northern blot analysis demonstrated C1 inhibitor mRNA to have a normal size, but its contents were reduced by about 50% compared with a normal subject. As the donor splice site is essential for an excising of the intron during mRNA processing, aberrant mRNA splicing may cause a rapid degradation of the transcript, thus resulting in the onset of hereditary angioneurotic edema.