Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology
Аутори
Parezanović, MarinaStojiljković, Maja
Anđelković, Marina
Stevanović, Nina
Spasovski, Vesna
Ugrin, Milena
Komazec, Jovana
Tošić, Nataša
Pavlović, Sonja
Celic, Dejan
Vučenović, Jelica
Skakić, Anita
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Background/Objectives: 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, the precise molecular-genetic diagnosis
and the earliest possible treatment are essential to avoid significant
disease progression.
Methods: 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.
Results: 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 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.
Conclusion: 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.
Извор:
European Journal of Human Genetic, 2023, 31, Supplement S1, 432-433Издавач:
- Springer Nature
Напомена:
- Abstracts from the 55th European Society of Human Genetics (ESHG) Conference
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Parezanović, Marina AU - Stojiljković, Maja AU - Anđelković, Marina AU - Stevanović, Nina AU - Spasovski, Vesna AU - Ugrin, Milena AU - Komazec, Jovana AU - Tošić, Nataša AU - Pavlović, Sonja AU - Celic, Dejan AU - Vučenović, Jelica AU - Skakić, Anita PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2277 AB - Background/Objectives: 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, the precise molecular-genetic diagnosis and the earliest possible treatment are essential to avoid significant disease progression. Methods: 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. Results: 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 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. Conclusion: 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 - Springer Nature C3 - European Journal of Human Genetic T1 - Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology EP - 433 IS - Supplement S1 SP - 432 VL - 31 DO - 10.1038/s41431-023-01339-3 ER -
@conference{ author = "Parezanović, Marina and Stojiljković, Maja and Anđelković, Marina and Stevanović, Nina and Spasovski, Vesna and Ugrin, Milena and Komazec, Jovana and Tošić, Nataša and Pavlović, Sonja and Celic, Dejan and Vučenović, Jelica and Skakić, Anita", year = "2023", abstract = "Background/Objectives: 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, the precise molecular-genetic diagnosis and the earliest possible treatment are essential to avoid significant disease progression. Methods: 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. Results: 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 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. Conclusion: 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 = "Springer Nature", journal = "European Journal of Human Genetic", title = "Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology", pages = "433-432", number = "Supplement S1", volume = "31", doi = "10.1038/s41431-023-01339-3" }
Parezanović, M., Stojiljković, M., Anđelković, M., Stevanović, N., Spasovski, V., Ugrin, M., Komazec, J., Tošić, N., Pavlović, S., Celic, D., Vučenović, J.,& Skakić, A.. (2023). Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology. in European Journal of Human Genetic Springer Nature., 31(Supplement S1), 432-433. https://doi.org/10.1038/s41431-023-01339-3
Parezanović M, Stojiljković M, Anđelković M, Stevanović N, Spasovski V, Ugrin M, Komazec J, Tošić N, Pavlović S, Celic D, Vučenović J, Skakić A. Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology. in European Journal of Human Genetic. 2023;31(Supplement S1):432-433. doi:10.1038/s41431-023-01339-3 .
Parezanović, Marina, Stojiljković, Maja, Anđelković, Marina, Stevanović, Nina, Spasovski, Vesna, Ugrin, Milena, Komazec, Jovana, Tošić, Nataša, Pavlović, Sonja, Celic, Dejan, Vučenović, Jelica, Skakić, Anita, "Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology" in European Journal of Human Genetic, 31, no. Supplement S1 (2023):432-433, https://doi.org/10.1038/s41431-023-01339-3 . .