Genotype phenotype correlation in a pediatric population with antithrombin deficiency
Нема приказа
Аутори
Kovač, MirjanaMitić, Gorana
Đilas, Iva
Kuzmanović, Milos
Serbić, Olivera
Leković, Danijela
Tomić, Branko
Bereczky, Zsuzsanna
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency. In 21% of the recruited families, mutations affecting exon 4, 5, and 6 of the SERPINC1 gene that causes type I AT deficiency were detected. In the remaining families, the mutation in exon 2 causing type II HBS (AT Budapest 3) was found. Thrombosis events were observed in 1 (33%) of those with type I, 11 (85%) of those with AT Budapest 3 in the homozygous respectively, and 1(33%) in the heterozygous form. Recurrent thrombosis was observed only in AT Budapest 3 in the homozygous form, in 27% during initi...al treatment of the first thrombotic event. Abdominal venous thrombosis and arterial ischemic stroke, observed in almost half of the children from the group with AT Budapest 3 in the homozygous form, were unprovoked in all cases. Conclusion: Type II HBS (AT Budapest 3) in the homozygous form is a strong risk factor for arterial and venous thrombosis in pediatric patients.What is Known:center dot Inherited AT deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1gene.center dot The genotype phenotype correlation in AT deficiency patients remains unclear, especially in pediatric patients.What is New:center dot The genetic results for our paediatric population predominantly showed the presence of a single specific mutation in exon 2, that causes type II HBS deficiency (AT Budapest 3).center dot In this group thrombosis mostly occurred as unprovoked, in almost half of them as abdominal thrombosis or stroke with high incidence of recurrent thrombosis, in 27% during initial treatment.
Кључне речи:
SERPINC1 mutations / Pediatric population / Antithrombin deficiencyИзвор:
European Journal of Pediatrics, 2019, 178, 10, 1471-1478Издавач:
- Springer, New York
Финансирање / пројекти:
- Комплексне болести као модел систем за проучавање модулације фенотипа-структурна и функционална анализа молекуларних биомаркера (RS-MESTD-Basic Research (BR or ON)-173008)
- Hungarian National Research Fund [OTKA K116228]
- Ministry of National Economy, Hungary [GINOP-2.3.2-15-2016-00039]
DOI: 10.1007/s00431-019-03433-5
ISSN: 0340-6199
PubMed: 31359133
WoS: 000484907200001
Scopus: 2-s2.0-85069908190
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Kovač, Mirjana AU - Mitić, Gorana AU - Đilas, Iva AU - Kuzmanović, Milos AU - Serbić, Olivera AU - Leković, Danijela AU - Tomić, Branko AU - Bereczky, Zsuzsanna PY - 2019 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1208 AB - Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency. In 21% of the recruited families, mutations affecting exon 4, 5, and 6 of the SERPINC1 gene that causes type I AT deficiency were detected. In the remaining families, the mutation in exon 2 causing type II HBS (AT Budapest 3) was found. Thrombosis events were observed in 1 (33%) of those with type I, 11 (85%) of those with AT Budapest 3 in the homozygous respectively, and 1(33%) in the heterozygous form. Recurrent thrombosis was observed only in AT Budapest 3 in the homozygous form, in 27% during initial treatment of the first thrombotic event. Abdominal venous thrombosis and arterial ischemic stroke, observed in almost half of the children from the group with AT Budapest 3 in the homozygous form, were unprovoked in all cases. Conclusion: Type II HBS (AT Budapest 3) in the homozygous form is a strong risk factor for arterial and venous thrombosis in pediatric patients.What is Known:center dot Inherited AT deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1gene.center dot The genotype phenotype correlation in AT deficiency patients remains unclear, especially in pediatric patients.What is New:center dot The genetic results for our paediatric population predominantly showed the presence of a single specific mutation in exon 2, that causes type II HBS deficiency (AT Budapest 3).center dot In this group thrombosis mostly occurred as unprovoked, in almost half of them as abdominal thrombosis or stroke with high incidence of recurrent thrombosis, in 27% during initial treatment. PB - Springer, New York T2 - European Journal of Pediatrics T1 - Genotype phenotype correlation in a pediatric population with antithrombin deficiency EP - 1478 IS - 10 SP - 1471 VL - 178 DO - 10.1007/s00431-019-03433-5 ER -
@article{ author = "Kovač, Mirjana and Mitić, Gorana and Đilas, Iva and Kuzmanović, Milos and Serbić, Olivera and Leković, Danijela and Tomić, Branko and Bereczky, Zsuzsanna", year = "2019", abstract = "Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency. In 21% of the recruited families, mutations affecting exon 4, 5, and 6 of the SERPINC1 gene that causes type I AT deficiency were detected. In the remaining families, the mutation in exon 2 causing type II HBS (AT Budapest 3) was found. Thrombosis events were observed in 1 (33%) of those with type I, 11 (85%) of those with AT Budapest 3 in the homozygous respectively, and 1(33%) in the heterozygous form. Recurrent thrombosis was observed only in AT Budapest 3 in the homozygous form, in 27% during initial treatment of the first thrombotic event. Abdominal venous thrombosis and arterial ischemic stroke, observed in almost half of the children from the group with AT Budapest 3 in the homozygous form, were unprovoked in all cases. Conclusion: Type II HBS (AT Budapest 3) in the homozygous form is a strong risk factor for arterial and venous thrombosis in pediatric patients.What is Known:center dot Inherited AT deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1gene.center dot The genotype phenotype correlation in AT deficiency patients remains unclear, especially in pediatric patients.What is New:center dot The genetic results for our paediatric population predominantly showed the presence of a single specific mutation in exon 2, that causes type II HBS deficiency (AT Budapest 3).center dot In this group thrombosis mostly occurred as unprovoked, in almost half of them as abdominal thrombosis or stroke with high incidence of recurrent thrombosis, in 27% during initial treatment.", publisher = "Springer, New York", journal = "European Journal of Pediatrics", title = "Genotype phenotype correlation in a pediatric population with antithrombin deficiency", pages = "1478-1471", number = "10", volume = "178", doi = "10.1007/s00431-019-03433-5" }
Kovač, M., Mitić, G., Đilas, I., Kuzmanović, M., Serbić, O., Leković, D., Tomić, B.,& Bereczky, Z.. (2019). Genotype phenotype correlation in a pediatric population with antithrombin deficiency. in European Journal of Pediatrics Springer, New York., 178(10), 1471-1478. https://doi.org/10.1007/s00431-019-03433-5
Kovač M, Mitić G, Đilas I, Kuzmanović M, Serbić O, Leković D, Tomić B, Bereczky Z. Genotype phenotype correlation in a pediatric population with antithrombin deficiency. in European Journal of Pediatrics. 2019;178(10):1471-1478. doi:10.1007/s00431-019-03433-5 .
Kovač, Mirjana, Mitić, Gorana, Đilas, Iva, Kuzmanović, Milos, Serbić, Olivera, Leković, Danijela, Tomić, Branko, Bereczky, Zsuzsanna, "Genotype phenotype correlation in a pediatric population with antithrombin deficiency" in European Journal of Pediatrics, 178, no. 10 (2019):1471-1478, https://doi.org/10.1007/s00431-019-03433-5 . .