SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE.

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209775%3A_____%2F22%3AN0000009" target="_blank" >RIV/00209775:_____/22:N0000009 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/22:00128685

Result on the web

<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361472/" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361472/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/falgy.2022.835503" target="_blank" >10.3389/falgy.2022.835503</a>

Result language

angličtina

Original language name

SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE.

Original language description

Hereditary angioedema with C1 Inhibitor deficiency (C1-INH-HAE) is caused by a constellation of variants of the SERPING1 gene (n = 809; 1,494 pedigrees), accounting for 86.8% of HAE families, showing a pronounced mutagenic liability of SERPING1 and pertaining to 5.6% de novo variants. C1-INH is the major control serpin of the kallikrein–kinin system (KKS). In addition, C1-INH controls complement C1 and plasminogen activation, both systems contributing to inflammation. Recognizing the failed control of C1s protease or KKS provides the diagnosis of C1-INH-HAE. SERPING1 variants usually behave in an autosomal-dominant character with an incomplete penetrance and a low prevalence. A great majority of variants (809/893; 90.5%) that were introduced into online database have been considered as pathogenic/likely pathogenic. Haploinsufficiency is a common feature in C1-INH-HAE where a dominant-negative variant product impacts the wild-type allele and renders it inactive. Small (36.2%) and large (8.3%) deletions/duplications are common, with exon 4 as the most affected one. Point substitutions with missense variants (32.2%) are of interest for the serpin structure–function relationship. Canonical splice sites can be affected by variants within introns and exons also (14.3%). For noncanonical sequences, exon skipping has been confirmed by splicing analyses of patients' blood-derived RNAs (n = 25). Exonic variants (n = 6) can affect exon splicing. Rare deep-intron variants (n = 6), putatively acting as pseudo-exon activating mutations, have been characterized as pathogenic. Some variants have been characterized as benign/likely benign/of uncertain significance (n = 74). This category includes some homozygous (n = 10) or compound heterozygous variants (n = 11). They are presenting with minor allele frequency (MAF) below 0.00002 (i.e., lower than C1-INH-HAE frequency), and may be quantitatively unable to cause haploinsufficiency. Rare benign variants could contribute as disease modifiers. Gonadal mosaicism in C1-INH-HAE is rare and must be distinguished from a de novo variant. Situations with paternal or maternal disomy have been recorded (n = 3). Genotypes must be interpreted with biological investigation fitting with C1-INH expression and typing. Any SERPING1 variant reminiscent of the dysfunctional phenotype of serpin with multimerization or latency should be identified as serpinopathy.

Czech name

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Czech description

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Type

J_ost - Miscellaneous article in a specialist periodical

CEP classification

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OECD FORD branch

30102 - Immunology

Project

<a href="/en/project/NV18-05-00330" target="_blank" >NV18-05-00330: Genetic determination of bradykinin-mediated angioedema severity in patients with hereditary angioedema</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in allergy

ISSN

2673-6101

e-ISSN

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Volume of the periodical

2

Issue of the periodical within the volume

MARCH 2022

Country of publishing house

CH - SWITZERLAND

Number of pages

17

Pages from-to

1-17

UT code for WoS article

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EID of the result in the Scopus database

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