TY  - 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 . .