1. Department of Dermatology, Institute of Clinical Medicine, University of Tsukuba, Ten-nodai, Tsukuba, Ibaraki, Japan
2. ^*Department of Dermatology, Dokkyo University School of Medicine, Kitakobayashi, Mibu, Tochigi, Japan

Correspondence: Dr Yasuhiro Kawachi, Department of Dermatology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1, Ten-nodai, Tsukuba, Ibaraki 305, Japan

Received 6 June 1997; Revised 30 November 1997; Accepted 7 January 1998.

Abstract

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 (TA) 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 C1 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.