Genetically determined heterogeneity of the C1 esterase inhibitor in patients with hereditary angioneurotic edema

Rosen, Fred S.; Alper, Chester A.; Pensky, Jack; Klemperer, Martin R.; Donaldson, Virginia H.

doi:10.1172/jci106708

Cited by 251 publications

(93 citation statements)

References 11 publications

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“…Hereditary angioedema (HAE, MIM# 106100) is an autosomal dominant disease due to alterations of the C1-inhibitor gene (C1 inh or C1NH; approved symbol, SERPING1; MIM# 606860) (Rosen et al, 1971;Tosi, 1998). Individuals affected by HAE have recurrent episodes of subcutaneous tissue swelling, particularly of the gastrointestinal mucosa, and the upper airways, that can be life threatening (Agostoni and Cicardi, 1992;Späth and Wuthrich, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Patients with type I HAE (approximately 85%) have low antigenic and functional C1 inhibitor levels. Patients with type II HAE (approximately 15%) have normal or elevated C1 inhibitor concentrations, with low C1 inhibitor functional activity caused by the secretion of a dysfunctional C1 inhibitor protein (Rosen et al 1965(Rosen et al , 1971.…”

Section: Introductionmentioning

confidence: 99%

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Detection of C1 inhibitor (SERPING1/C1NH) mutations in exon 8 in patients with hereditary angioedema: evidence for 10 novel mutations

et al. 2002

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Hereditary angioedema (HAE) is caused by mutations in the C1 inhibitor gene (SERPING1, C1NH) and the result is C1 inhibitor deficiency, either in levels or function. We have searched exon 8 for mutations by direct sequencing and analyzed the rest of the exons by SSCP in 87 Spanish families affected by HAE. Out of 87 screened families, we have detected exon 8 mutations in 26. Among these, 17 different mutations were identified: 14 point mutations and 3 frameshift. Seven of the point mutations and the three frameshift were not previously reported. Mutations were: S438P; R444P; V451G; W460X; V468D; G471E; X479R; S417fsX427; I440fsX450; E429fsX450. The rest of the families presented previously reported mutations, 5 missense and two nonsense. In none of the 26 families was an additional change identified in the rest of the exons by SSCP, and, in 20 out of the 22 families with p oint mutation, we verified that the mutation did not affect a healthy relative. Seven of these families had no history of the disease, and in five of them we were able to verify that the progenitors did not have the mutation. Therefore, they were de novo mutations.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Detection of C1 inhibitor (SERPING1/C1NH) mutations in exon 8 in patients with hereditary angioedema: evidence for 10 novel mutations

et al. 2002

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“…C1INH also plays an important role in the regulation of other serine proteases (MASP-1, MASP-2, Factor XIIa, Factor XIa, kallikrein, plasmin, and thrombin) [Davis et al, 1986]. According to the antigenic plasma level of the C1INH protein, two types of HAE are distinguished: a quantitative defect (type I) in which the protein level is low, and a qualitative defect (type II), which is less frequent and characterized by decreased functional activity, in spite of normal or even high antigenic levels [Rosen et al, 1971]. The high incidence of de novo mutations (~25%) [Verpy et al, 1996, Pappalardo et al, 2000, and the variability of C1INH protein levels in young subjects underscore the importance of DNA assays to provide direct and rapid diagnosis for suspected HAE-cases.…”

Section: Introductionmentioning

confidence: 99%

Mutation screening of the C1 inhibitor gene among Hungarian patients with hereditary angioedema

Kalmár¹,

Bors²,

Farkas

et al. 2003

Hum. Mutat.

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Hereditary angioneurotic edema (HAE) is an autosomal dominant disorder characterized by episodic local subcutaneous and submucosal edema caused by the deficiency of activated C1 esterase inhibitor protein (C1-INH, type I (C1NH): reduced serum antigen level, type II: reduced activity and normal serum antigen level). The aim of the present study was to determine the disease-causing mutations in the C1INH gene (SERPING1) among Hungarian HAE-patients. The estimated number of affected HAE-families in Hungary is 40-50, out of which 26 families (type I:23, type II:3) managed in a single center were enrolled in the current study. To detect large deletions/insertions, we used Southern-blotting analysis followed by real time PCR based gene dosage analysis. In the absence of large structural changes, we employed direct sequencing covering the whole coding region and splicing sites of the C1INH gene. Large deletions were detected in 4/23 (17.4%) type I families. We found the g.16788C>T (p.Arg444Cys) mutation in each 3, type II HAE-families. In the remaining type

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“…As originally noted by Rosen (9) and independently by Laurell (lo), some of the patients with the abnormal variant protein have a Cl inhibitor which is unusually heavy in molecular weight and is bound in serum to albumin. Thus they have an antigenetically normal, functionless protein which is bound to serum albumin.…”

Section: Effect Of Sex Hormones On the Hereditary Angioedema Complemementioning

confidence: 82%

Effect of sex hormones on the complement‐related clinical disorder of hereditary angioedema

Frank

1979

Arthritis & Rheumatism

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Genetically determined heterogeneity of the C1 esterase inhibitor in patients with hereditary angioneurotic edema

Cited by 251 publications

References 11 publications

Detection of C1 inhibitor (SERPING1/C1NH) mutations in exon 8 in patients with hereditary angioedema: evidence for 10 novel mutations

Detection of C1 inhibitor (SERPING1/C1NH) mutations in exon 8 in patients with hereditary angioedema: evidence for 10 novel mutations

Mutation screening of the C1 inhibitor gene among Hungarian patients with hereditary angioedema

Effect of sex hormones on the complement‐related clinical disorder of hereditary angioedema

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