Functional studies associate novel DUOX2 gene variants detected in heterozygosity to Crohn’s disease

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00585142" target="_blank" >RIV/68378050:_____/24:00585142 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/24:10478340 RIV/00216208:11130/24:10478340

Result on the web

<a href="https://link.springer.com/article/10.1007/s11033-024-09317-8" target="_blank" >https://link.springer.com/article/10.1007/s11033-024-09317-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s11033-024-09317-8" target="_blank" >10.1007/s11033-024-09317-8</a>

Result language

angličtina

Original language name

Functional studies associate novel DUOX2 gene variants detected in heterozygosity to Crohn’s disease

Original language description

Purpose: Crohn’s disease is a chronic gastrointestinal inflammatory disease with possible extraintestinal symptoms. There are predisposing genetic factors and even monogenic variants of the disorder. One of the possible genetic factors are variants of the DUOX2 gene. The protein product of the DUOX2 gene is a dual oxidase enzyme producing H2O2 in the bowel. Reduced H2O2 levels impact mucosal homeostasis and contribute to the development of inflammatory bowel disease. Thus far, only 19 patients with IBD with the DUOX2 variants have been described. Methods: Here we present a case report of an adolescent female diagnosed at eleven years of age with IBD that was subsequently reclassified as Crohn’s disease. She was treated with immunosuppressants and biological therapy but experienced additional complications. Her peripheral blood lymphocyte DNA was studied using massive parallel sequencing. Detected variants were functionally studied. Results: Whole exome sequencing found two novel DUOX2 gene variants: a de novo variant c.3646C>T, p.R1216W and a maternally inherited variant c.3391G>A, p.A1131T which were initially classified as variants of unknown significance. However, follow-up functional studies demonstrated that both DUOX2 variants led to impaired H2O2 generation, which led to their reclassification to the likely pathogenic class according to the ACMG.net. Therefore, we conclude that these variants are causative for the disease. Conclusions: Identifying novel variants in patients with Crohn’s disease and their families is important for precision medicine approaches and understanding of the pathogenesis of likely “monogenic” rare forms of inflammatory bowel disease.

Czech name

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Czech description

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Type

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

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LM2018132" target="_blank" >LM2018132: The National Center for Medical Genomic</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

Molecular Biology Reports

ISSN

0301-4851

e-ISSN

1573-4978

Volume of the periodical

51

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

7

Pages from-to

399

UT code for WoS article

001178229900007

EID of the result in the Scopus database

2-s2.0-85187176218