dc.contributor | Morić, Ivana | |
dc.contributor | Đorđević, Valentina | |
dc.creator | Skakić, Anita | |
dc.creator | Parezanović, Marina | |
dc.creator | Pavlović, Đorđe | |
dc.creator | Srevanović, Nina | |
dc.creator | Anđelković, Marina | |
dc.creator | Klaassen, Kristel | |
dc.creator | Ugrin, Milena | |
dc.creator | Komazec, Jovana | |
dc.creator | Spasovski, Vesna | |
dc.creator | Đorđević, Maja | |
dc.creator | Pavlović, Sonja | |
dc.creator | Stojiljković, Maja | |
dc.date.accessioned | 2024-07-24T21:57:16Z | |
dc.date.available | 2024-07-24T21:57:16Z | |
dc.date.issued | 2024 | |
dc.identifier.isbn | 978-86-82679-16-5 | |
dc.identifier.uri | www.belbi.bg.ac.rs | |
dc.identifier.uri | https://imagine.imgge.bg.ac.rs/handle/123456789/2457 | |
dc.description.abstract | University of Belgrade, Serbia
anita.skakic@imgge.bg.ac.rs
Glycogen Storage Disease Ib (GSD Ib) is a rare metabolic disorder characterized by a deficiency
of glucose-6-phosphate translocase, leading to metabolic disruptions and neutropenia.
Varying severity and progression of neutropenia were detected among individuals with the
same genotype, indicating a complex genotype-phenotype correlation. We aim to explore
potential modifier genes influencing neutropenia in GSD Ib, focusing on five patients with
the homozygous c.1042_1043delCT variant in the SLC37A4 gene. These patients exhibit
diverse neutropenia profiles, with two displaying mild and intermittent neutropenia, while
the remaining three develop severe and persistent neutropenia.
Whole genome sequencing (MGISEQ-G400, BGITech) was conducted on five unrelated
subjects, all presenting with previously identified pathogenic homozygous SLC37A4 variant.
We followed GATK best practices for genomic data processing to identify genetic variations
associated with observed clinical differences. A unique pipeline was constructed focusing
on neutropenia-related genes and genes involved in glucose-6-phosphate metabolism,
neutrophil function pathways, immune system regulation, ER stress, and UPR response.
In patients with severe neutropenia, we identified two heterozygous variants (c.-70G>C and
c.96T>C, p.Thr32Thr) in the JAGN1 gene, which is essential for neutrophil differentiation.
Additionally, severe neutropenia patients had variants in CTLA4 (c.49A>G, p.Thr17Ala) and
TGFB1 (c.29C>T, p.Pro10Leu), genes involved in immune regulation and cell survival and which
have previously been recognized as modifier genes in various immunological conditions.
This research underscores the potential significance of modifier genes in shaping the diverse
course of neutropenia in GSD Ib, highlighting the need for further functional studies to
elucidate the precise roles of these variants in disease presentation. Investigating potential
genetic modifiers can provide valuable insights into the molecular base of the disease and
guide future research focused on developing customized therapeutic approaches for the
specific neutropenic phenotype. | sr |
dc.language.iso | en | sr |
dc.publisher | Belgrade : Institute of Molecular Genetics and Genetic Engineering | sr |
dc.relation | info:eu-repo/grantAgreement/ScienceFundRS/Prizma2023_PM/6999/RS// | sr |
dc.rights | openAccess | sr |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | 5th Belgrade Bioinformatics Conference | sr |
dc.subject | GSD Ib | sr |
dc.subject | WGS | sr |
dc.subject | modifier genes | sr |
dc.title | WGS approach to identify potential genetic modifiers in Glycogen Storage Disease Ib | sr |
dc.type | conferenceObject | sr |
dc.rights.license | BY-NC-ND | sr |
dc.citation.epage | 72 | |
dc.citation.spage | 72 | |
dc.description.other | Book of abstracts: 5th Belgrade Bioinformatics Conference, Serbia, Belgrade,17-20 june 2024. | sr |
dc.identifier.fulltext | https://imagine.imgge.bg.ac.rs/bitstream/id/845706/BelBi2024-Book-of-Abstracts_1-16,88,141-142.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_imagine_2457 | |
dc.type.version | publishedVersion | sr |