Identification of a new P1 residue mutation (444Arg→Ser) in a dysfunctional C1 inhibitor protein contained in a type II hereditary angioedema plasma

@article{Aulak1990IdentificationOA,
  title={Identification of a new P1 residue mutation (444Arg→Ser) in a dysfunctional C1 inhibitor protein contained in a type II hereditary angioedema plasma},
  author={Kulwant Singh Aulak and Marco Cicardi and Richard A. Harrison},
  journal={FEBS Letters},
  year={1990},
  volume={266}
}
A new reactive‐centre P1 residue mutation (444Arg→Ser), has been identified in a dysfunctional C1 inhibitor protein, C1 inhibitor(Ba), contained in a type II hereditary angioedema plasma. This substitution is compatible with a point mutation of the 444Arg codon (CGC→AGC), and represents the first non‐histidine, non‐cysteine P1 residue mutant described for C1 inhibitor. 
A dysfunctional Cl inhibitor protein with a new reactive center mutation (Arg‐444→Leu)
TLDR
A Pl mutation was identified in a dysfunctional Cl inhibitor from a patient with type 2 hereditary angioneurotic edema and was defined at the level of the protein, the mRNA, and the mRNA.
A review of the reported defects in the human C1 esterase inhibitor gene producing hereditary angioedema including four new mutations.
TLDR
The DNA from HAE patients is sequenced and four previously unreported mutations are discovered, including a splice site error and a missense error present in the eighth exon of the C1INH.
A Mutation Unique in Serine Protease Inhibitors (Serpins) Identified in a Family with Type II Hereditary Angioneurotic Edema
TLDR
This work reports the first molecular defect characterized in a Spanish family with type II HANE, and to date, this is the first reported mutation at the P-1′ site of the reactive center in individuals with type Two HANE.
Unique C1 inhibitor dysfunction in a kindred without angioedema. II. Identification of an Ala443-->Val substitution and functional analysis of the recombinant mutant protein.
TLDR
The Ala443-->Val mutation converts C1 inhibitor from a substrate to an inhibitor of trypsin, and the role of the P2 residue in the determination of target protease specificity is emphasized.
Mutation screening of C1 inhibitor gene in 108 unrelated families with hereditary angioedema: functional and structural correlates.
TLDR
A large number of new mutations related to HAE are identified providing additional evidence of the genetic heterogeneity of this disease and point toward particular amino acid residues important for protein function that may represent mutation hot spots.
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TLDR
This represents the first report of a nucleotide insertion in the C1-inhibitor gene causing type II HAE.
C1-inhibitor deficiency and angioedema.
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Effective therapies can prevent or revert angioedema symptoms in C1-Inh deficiency, the main problem of this condition remaining misdiagnosis.
Molecular genetics of C1-inhibitor and hereditary angiooedema
TLDR
The hereditary transmission of angioneurotic oedema was documented as early as 1888 by the remarkable pedigree investigations of W. Osier, which led to the recognition of the autosomal dominant mode of transmission of the disease.
Crucial residues in the carboxy-terminal end of C1 inhibitor revealed by pathogenic mutants impaired in secretion or function.
TLDR
Data point to a key role of certain residues in the conserved COOH-terminal region of serpins in determining the protein foldings compatible with transport and proper exposure of the reactive site loop in angioedema patients.
Mutational spectrum and geno‐phenotype correlation in Chinese families with Hereditary Angioedema
TLDR
A Chinese genetic database of hereditary angioedema is established and the potential correlation between genotype and phenotype seems not to exist.
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Dysfunctional C1-inhibitor(At), isolated from a type II hereditary-angio-oedema plasma, contains a P1 'reactive centre' (Arg444----His) mutation.
Simple rapid procedures for identification and analysis of dysfunctional C1-inhibitor proteins mutated at the reactive-centre P1 residue have been developed and used to define structurally a
Type II hereditary angioneurotic edema that may result from a single nucleotide change in the codon for alanine-436 in the C1 inhibitor gene.
Identical single-base changes in the C1 inhibitor gene that may result in dysfunctional inhibitor proteins are described in two different families with type II hereditary angioneurotic edema.
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TLDR
The presence of CpG dinucleotides in the codons specifying the P1 arginines of C1 inhibitor and antithrombin III explains the high incidence of histidine and cysteine substitutions observed among dysfunctional mutants of these serine protease inhibitors.
A novel amino acid substitution in the reactive site of a congenital variant antithrombin. Antithrombin pescara, ARG393 to pro, caused by a CGT to CCT mutation.
TLDR
It is demonstrated that the molecular defect of antithrombin Pescara is caused by a CGT to CCT mutation in codon 393, which may be of broad interest, as other members of the serine protease inhibitor superfamily contain arginine at their reactive sites and may be expected to undergo a similar mutation.
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TLDR
Serums of patients with hereditary angioneurotic edema lack inhibitory activity against the esterase derived from the first component of complement, whereas in another group of patients an abnormal, nonfunctional protein is synthesized.
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TLDR
Evidence suggests that absence of serum inhibitor of C′1-esterase is an inherited abnormality in those with the familial type of angioneurotic edema, and this determination may permit identification of young family members who will have attacks of swelling later in life.
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TLDR
Study of a 33-year-old Caucasian woman with hereditary angioneurotic edema and her two sons have revealed that the inborn biochemical lesion is likely an inherited deficiency of serum inhibitor to plasma kallikrein and/or serum globulin permeability factor.
Behavior in vivo of normal and dysfunctional C1 inhibitor in normal subjects and patients with hereditary angioneurotic edema.
TLDR
The lower than anticipated levels of C1 inhibitor in HANE type 1 appears to result from (a) the single functional gene and (b) increased catabolism of the protein, perhaps related to activation of C 1 or other proteases.
Altered specificities of genetically engineered α1 antitrypsin variants
Seven active site variants of human alpha 1-antitrypsin (alpha 1AT) were produced in Escherichia coli following site-specific mutagenesis of the alpha 1AT complementary DNA. alpha 1AT (Ala358), alpha
Single amino acid substitutions in the reactive site of antithrombin leading to thrombosis. Congenital substitution of arginine 393 to cysteine in antithrombin Northwick Park and to histidine in antithrombin Glasgow.
TLDR
Two novel tryptic peptides of molecular mass (M + H)+ 2976 and 2952 were identified in the digests of antithrombin Northwick Park and Glasgow, respectively, which comprised the amino acid sequence Ala371-Arg399, but with single amino acid substitutions at the reactive site.
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