Use this URL to cite or link to this record in EThOS:
Title: The genetic basis of C1 inhibitor deficiency and hereditary angioedema
Author: Cumming, S. A.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2002
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
Hereditary angioedema (HAE) is characterised by recurrent episodes of acute swelling in localised areas of the skin, mucous membranes or internal organs. Death from laryngeal oedema is a constant threat. HAE results from mutations within the C1 inhibitor gene leading to a plasma deficiency of C1 inhibitor. It can be divided into two phenotypic groups: Type I which is characterised by a low plasma level of normal C1 inhibitor and Type II which is characterised by normal or elevated plasma level of a dysfunctional mutant. The focus of my study was to determine the genotype-phenotype relationship of mutations identified in families of patients suffering from HAE. Exons of the C1 inhibitor gene were sequenced in 27 patients with HAE. This identified 2 point mutations, a splice site mutation and 3 polymorphisms. The effect of one polymorphism, V458M, on the function of C1 inhibitor was characterised. It had no effect on C1 inhibitor function or the level of the protein in a normal, healthy control group. No abnormalities could be detected in 14 individuals with HAE. The DNA from these individuals was examined by quantitative PCR to detect exon deletions. Deletions of exons IV, V and VI were detected in two patients and exon VII and VIII in four patients. The point mutation and exon deletions were then mapped onto families with HAE secondary to C1 inhibitor deficiency. This allowed the families to be classified into three groups. i) families with HAE who had a mutation in exon II of C1 inhibitor and a deletion or second point mutation in trans, ii) families with a single point mutation, splice site mutation or deletion in C1 inhibitor and iii) families with HAE with no abnormality within the coding region of the C1 inhibitor gene. This thesis presents a detailed analysis of the genetic basis of C1 inhibitor deficiency in families with HAE.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available