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SERPING1 variants and C1-INH biological function [Elektronski vir] : a close relationship with C1-INH-HAEDrouet, Christian ...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.Vir: Frontiers in allergy. - ISSN 2673-6101 (Vol. 3, 31 Mar. 2022, str. 1-17)Vrsta gradiva - e-članek ; neleposlovje za odrasleLeto - 2022Jezik - angleškiCOBISS.SI-ID - 103075331
Avtor
Drouet, Christian |
López Lera, Alberto |
Ghannam, Arije |
López-Trascasa, Margarita |
Cichon, Sven |
Ponard, Denise |
Parsopoulou, Faidra |
Grombirikova, Hana |
Freiberger, Tomas |
Rijavec, Matija |
Lopes Veronez, Camila |
Pesquero, João Bosco |
Germenis, Anastasios E.
Teme
Angioedemas, hereditary |
Genetics |
Diagnosis |
Genetic variation |
Serpins |
Hereditarni angioedemi |
Genetika |
Diagnostika |
Genetska raznolikost |
Serpini |
SERPING1 gene |
C1-INH |
C1-INH-HAE |
C1 inhibitor |
serpinopathy |
gen SERPING1 |
C1-INH |
C1-INH-HAE |
zaviralec C1 |
serpinopatija
Vnos na polico
Trajna povezava
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Faktor vpliva
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Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Drouet, Christian | |
López Lera, Alberto | |
Ghannam, Arije | |
López-Trascasa, Margarita | |
Cichon, Sven | |
Ponard, Denise | |
Parsopoulou, Faidra | |
Grombirikova, Hana | |
Freiberger, Tomas | |
Rijavec, Matija | 29300 |
Lopes Veronez, Camila | |
Pesquero, João Bosco | |
Germenis, Anastasios E. |
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