High-risk population screening for fabry disease in patients with chronic renal failure of unknown etiology
Аутори
Parezanović, MarinaAnđelković, Marina
Stevanović, Nina
Spasovski, Vesna
Ugrin, Milena
Komazec, Jovana
Klaassen, Kristel
Stanković, Sara
Pavlović, Sonja
Stojiljković, Maja
Skakić, Anita
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Fabry disease (FD) is a rare X-linked disorder caused by variants in the GLA gene leading to the
deficiency of lysosomal α-galactosidase-A and progressive accumulation of globotriaosylceramide
affecting the heart, nervous system, and kidneys. FD has overlapping phenotypes and often remains
undiagnosed. Therefore, a precise molecular-genetic diagnosis and the earliest possible treatment are
essential to avoid significant disease progression. The study aimed to determine the strategy for
establishing routine molecular genetic diagnostics of FD in Serbia to provide an early application of
appropriate therapy and genetic advice to families with a high risk for the birth of a child with FD. We
analyzed 95 (34 female and 61 male) hemodialysis patients with clinical suspicion of FD using Sanger
sequencing of all coding exons (7) and flanking intron regions of the GLA gene and measured the
relative expression of the GLA gene in available samples. The genetic analysis revealed 3 patien...ts with
a missense variant (p.Asp313Tyr), and 10 patients with combinations of non-coding variants, described
as complex intronic haplotypes (CIHs). CIH1 (c.-10C>T, c.370-81_370-77delCAGCC, c.640-16A>G,
c.1000-22C>T), the most frequent haplotype, was detected in 7 (7.4%) patients. Lyso-Gb3 biomarker
levels were within the normal range in each tested patient. However, RT-qPCR analysis revealed
decreased relative expression of the GLA gene in PBMC of 2 female patients with CIH1 and one
female patient carrying only c.-10C>T variant by 9,1%, 7,4%, 46,3%, respectively, pointing out that
further analyses are needed to confirm/exclude FD in these patients. Because the effects of CIHs are not
yet fully understood, our work highlights the importance of analyzing intronic regions of the GLA gene
as genetic modifiers and the need to include expression analysis in the diagnostic algorithm.
Кључне речи:
fabry disease / precise molecular-genetic diagnosis / high-risk population screeningИзвор:
Genetics & Applications, 2023, 7, 2 (Special edition)Издавач:
- Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo
Напомена:
- Book of abstracts: International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina - ABMBBIH May, 2023
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Parezanović, Marina AU - Anđelković, Marina AU - Stevanović, Nina AU - Spasovski, Vesna AU - Ugrin, Milena AU - Komazec, Jovana AU - Klaassen, Kristel AU - Stanković, Sara AU - Pavlović, Sonja AU - Stojiljković, Maja AU - Skakić, Anita PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1901 AB - Fabry disease (FD) is a rare X-linked disorder caused by variants in the GLA gene leading to the deficiency of lysosomal α-galactosidase-A and progressive accumulation of globotriaosylceramide affecting the heart, nervous system, and kidneys. FD has overlapping phenotypes and often remains undiagnosed. Therefore, a precise molecular-genetic diagnosis and the earliest possible treatment are essential to avoid significant disease progression. The study aimed to determine the strategy for establishing routine molecular genetic diagnostics of FD in Serbia to provide an early application of appropriate therapy and genetic advice to families with a high risk for the birth of a child with FD. We analyzed 95 (34 female and 61 male) hemodialysis patients with clinical suspicion of FD using Sanger sequencing of all coding exons (7) and flanking intron regions of the GLA gene and measured the relative expression of the GLA gene in available samples. The genetic analysis revealed 3 patients with a missense variant (p.Asp313Tyr), and 10 patients with combinations of non-coding variants, described as complex intronic haplotypes (CIHs). CIH1 (c.-10C>T, c.370-81_370-77delCAGCC, c.640-16A>G, c.1000-22C>T), the most frequent haplotype, was detected in 7 (7.4%) patients. Lyso-Gb3 biomarker levels were within the normal range in each tested patient. However, RT-qPCR analysis revealed decreased relative expression of the GLA gene in PBMC of 2 female patients with CIH1 and one female patient carrying only c.-10C>T variant by 9,1%, 7,4%, 46,3%, respectively, pointing out that further analyses are needed to confirm/exclude FD in these patients. Because the effects of CIHs are not yet fully understood, our work highlights the importance of analyzing intronic regions of the GLA gene as genetic modifiers and the need to include expression analysis in the diagnostic algorithm. PB - Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo C3 - Genetics & Applications T1 - High-risk population screening for fabry disease in patients with chronic renal failure of unknown etiology IS - 2 (Special edition) IS - 107 VL - 7 UR - https://hdl.handle.net/21.15107/rcub_imagine_1901 ER -
@conference{ author = "Parezanović, Marina and Anđelković, Marina and Stevanović, Nina and Spasovski, Vesna and Ugrin, Milena and Komazec, Jovana and Klaassen, Kristel and Stanković, Sara and Pavlović, Sonja and Stojiljković, Maja and Skakić, Anita", year = "2023", abstract = "Fabry disease (FD) is a rare X-linked disorder caused by variants in the GLA gene leading to the deficiency of lysosomal α-galactosidase-A and progressive accumulation of globotriaosylceramide affecting the heart, nervous system, and kidneys. FD has overlapping phenotypes and often remains undiagnosed. Therefore, a precise molecular-genetic diagnosis and the earliest possible treatment are essential to avoid significant disease progression. The study aimed to determine the strategy for establishing routine molecular genetic diagnostics of FD in Serbia to provide an early application of appropriate therapy and genetic advice to families with a high risk for the birth of a child with FD. We analyzed 95 (34 female and 61 male) hemodialysis patients with clinical suspicion of FD using Sanger sequencing of all coding exons (7) and flanking intron regions of the GLA gene and measured the relative expression of the GLA gene in available samples. The genetic analysis revealed 3 patients with a missense variant (p.Asp313Tyr), and 10 patients with combinations of non-coding variants, described as complex intronic haplotypes (CIHs). CIH1 (c.-10C>T, c.370-81_370-77delCAGCC, c.640-16A>G, c.1000-22C>T), the most frequent haplotype, was detected in 7 (7.4%) patients. Lyso-Gb3 biomarker levels were within the normal range in each tested patient. However, RT-qPCR analysis revealed decreased relative expression of the GLA gene in PBMC of 2 female patients with CIH1 and one female patient carrying only c.-10C>T variant by 9,1%, 7,4%, 46,3%, respectively, pointing out that further analyses are needed to confirm/exclude FD in these patients. Because the effects of CIHs are not yet fully understood, our work highlights the importance of analyzing intronic regions of the GLA gene as genetic modifiers and the need to include expression analysis in the diagnostic algorithm.", publisher = "Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo", journal = "Genetics & Applications", title = "High-risk population screening for fabry disease in patients with chronic renal failure of unknown etiology", number = "2 (Special edition), 107", volume = "7", url = "https://hdl.handle.net/21.15107/rcub_imagine_1901" }
Parezanović, M., Anđelković, M., Stevanović, N., Spasovski, V., Ugrin, M., Komazec, J., Klaassen, K., Stanković, S., Pavlović, S., Stojiljković, M.,& Skakić, A.. (2023). High-risk population screening for fabry disease in patients with chronic renal failure of unknown etiology. in Genetics & Applications Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo., 7(2 (Special edition)). https://hdl.handle.net/21.15107/rcub_imagine_1901
Parezanović M, Anđelković M, Stevanović N, Spasovski V, Ugrin M, Komazec J, Klaassen K, Stanković S, Pavlović S, Stojiljković M, Skakić A. High-risk population screening for fabry disease in patients with chronic renal failure of unknown etiology. in Genetics & Applications. 2023;7(2 (Special edition)). https://hdl.handle.net/21.15107/rcub_imagine_1901 .
Parezanović, Marina, Anđelković, Marina, Stevanović, Nina, Spasovski, Vesna, Ugrin, Milena, Komazec, Jovana, Klaassen, Kristel, Stanković, Sara, Pavlović, Sonja, Stojiljković, Maja, Skakić, Anita, "High-risk population screening for fabry disease in patients with chronic renal failure of unknown etiology" in Genetics & Applications, 7, no. 2 (Special edition) (2023), https://hdl.handle.net/21.15107/rcub_imagine_1901 .