title: A novel donor splice site mutation in the C1 inhibitor gene of a patient with type I hereditary angioneurotic edema.
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 (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 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.
authors.affiliation: Department of Dermatology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kawachi
authors.forename: T
authors.initials: T
authors.lastname: Hibi
authors.forename: S
authors.initials: S
authors.lastname: Yamazaki
authors.forename: F
authors.initials: F
authors.lastname: Otsuka
mesh_terms: D000328:Adult; D000483:Alleles; D000799:Angioedema / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D006801:Humans; D017354:Point Mutation / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D015842:Serine Proteinase Inhibitors / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors