Deep Intronic Mutation in SERPING1 Caused Hereditary Angioedema Through Pseudoexon Activation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F20%3A00072618" target="_blank" >RIV/00159816:_____/20:00072618 - isvavai.cz</a>

Alternative codes found

RIV/00209775:_____/20:N0000005 RIV/00216224:14110/20:00118619

Result on the web

<a href="https://link.springer.com/article/10.1007%2Fs10875-020-00753-2" target="_blank" >https://link.springer.com/article/10.1007%2Fs10875-020-00753-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10875-020-00753-2" target="_blank" >10.1007/s10875-020-00753-2</a>

Result language

angličtina

Original language name

Deep Intronic Mutation in SERPING1 Caused Hereditary Angioedema Through Pseudoexon Activation

Original language description

Purpose Hereditary angioedema (HAE) is a rare autosomal dominant life-threatening disease characterized by low levels of C1 inhibitor (type I HAE) or normal levels of ineffective C1 inhibitor (type II HAE), typically occurring as a consequence of a SERPING1 mutation. In some cases, a causal mutation remains undetected after using a standard molecular genetic analysis. Results Here we show a long methodological way to the final discovery of c.1029 + 384A &gt; G, a novel deep intronic mutation in intron 6 which is responsible for HAE type I in a large family and has not been identified by a conventional diagnostic approach. This mutation results in de novo donor splice site creation and subsequent pseudoexon inclusion, the mechanism firstly described to occur in SERPING1 in this study. We additionally discovered that the proximal part of intron 6 is a region potentially prone to pseudoexon-activating mutations, since natural alternative exons and additional cryptic sites occur therein. Indeed, we confirmed the existence of at least two different alternative exons in this region not described previously. Conclusions In conclusion, our results suggest that detecting aberrant transcripts, which are often low abundant because of nonsense-mediated decay, requires a modified methodological approach. We suggest SERPING1 intron 6 sequencing and/or tailored mRNA analysis to be routinely used in HAE patients with no mutation identified in the coding sequence.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30102 - Immunology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2020

Confidentiality

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

Name of the periodical

Journal of Clinical Immunology

ISSN

0271-9142

e-ISSN

—

Volume of the periodical

40

Issue of the periodical within the volume

3

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

435-446

UT code for WoS article

000524860800002

EID of the result in the Scopus database

—