Publication

The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension

Haarman, M. G., Kerstjens-Frederikse, W. S., Vissia-Kazemier, T. R., Breeman, K. T. N., Timens, W., Vos, Y. J., Roofthooft, M. T. R., Hillege, H. L. & Berger, R. M. F., Oct-2020, In : The Journal of Pediatrics. 225, p. 65-+ 14 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Haarman, M. G., Kerstjens-Frederikse, W. S., Vissia-Kazemier, T. R., Breeman, K. T. N., Timens, W., Vos, Y. J., Roofthooft, M. T. R., Hillege, H. L., & Berger, R. M. F. (2020). The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension. The Journal of Pediatrics, 225, 65-+. https://doi.org/10.1016/j.jpeds.2020.05.051

Author

Haarman, Meindina G ; Kerstjens-Frederikse, Wilhelmina S ; Vissia-Kazemier, Theresia R ; Breeman, Karel T N ; Timens, Wim ; Vos, Yvonne J ; Roofthooft, Marc T R ; Hillege, Hans L ; Berger, Rolf M F. / The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension. In: The Journal of Pediatrics. 2020 ; Vol. 225. pp. 65-+.

Harvard

Haarman, MG, Kerstjens-Frederikse, WS, Vissia-Kazemier, TR, Breeman, KTN, Timens, W, Vos, YJ, Roofthooft, MTR, Hillege, HL & Berger, RMF 2020, 'The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension', The Journal of Pediatrics, vol. 225, pp. 65-+. https://doi.org/10.1016/j.jpeds.2020.05.051

Standard

The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension. / Haarman, Meindina G; Kerstjens-Frederikse, Wilhelmina S; Vissia-Kazemier, Theresia R; Breeman, Karel T N; Timens, Wim; Vos, Yvonne J; Roofthooft, Marc T R; Hillege, Hans L; Berger, Rolf M F.

In: The Journal of Pediatrics, Vol. 225, 10.2020, p. 65-+.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Haarman MG, Kerstjens-Frederikse WS, Vissia-Kazemier TR, Breeman KTN, Timens W, Vos YJ et al. The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension. The Journal of Pediatrics. 2020 Oct;225:65-+. https://doi.org/10.1016/j.jpeds.2020.05.051


BibTeX

@article{7ec9f150bc8f4b46b26ae6e0a57a4842,
title = "The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension",
abstract = "Objective To describe the prevalence of pulmonary arterial hypertension (PAH)-associated gene mutations, and other genetic characteristics in a national cohort of children with PAH from the Dutch National registry and to explore genotype-phenotype associations and outcomes.Study design Children (n = 70) diagnosed with idiopathic PAH, heritable PAH, PAH associated with congenital heart disease with coincidental shunt (PAH-congenital heart disease group 3), PAH after closure of a cardiac shunt (PAH-congenital heart disease group 4), or PAH associated with other noncardiac conditions were enrolled. Targeted next-generation sequencing was performed on PAH-associated genes (BMPR2, ACVRL1 , EIF2AK4, CAV1 , ENG, KCNK3, SMAD9, and TBX4). Also, children were tested for specific genetic disorders in case of clinical suspicion. Additionally, children were tested for copy number variations.Results Nineteen children (27%) had a PAH-associated gene mutation/variant: BMPR2 n = 7, TBX4 n = 8, ACVRL1 n = 1, KCNK3 n = 1, and EIF2AK4 n = 2. Twelve children (17%) had a genetic disorder with an established association with PAH (including trisomy 21 and cobalamin C deficiency). In another 16 children (23%), genetic disorders without an established association with PAH were identified (including Noonan syndrome, Beals syndrome, and various copy number variations). Survival rates differed between groups and was most favorable in TBX4 variant carriers.Conclusions Children with PAH show a high prevalence of genetic disorders, not restricted to established PAH-associated genes. Genetic architecture could play a role in risk-stratified care management in pediatric PAH.",
keywords = "ACTA2 MUTATION, BMPR2, TBX4, POLYCYTHEMIA, ASSOCIATION, GUIDELINES, MANAGEMENT, PHENOTYPE, CONSENSUS, VARIANTS",
author = "Haarman, {Meindina G} and Kerstjens-Frederikse, {Wilhelmina S} and Vissia-Kazemier, {Theresia R} and Breeman, {Karel T N} and Wim Timens and Vos, {Yvonne J} and Roofthooft, {Marc T R} and Hillege, {Hans L} and Berger, {Rolf M F}",
note = "Copyright {\textcopyright} 2020 Elsevier Inc. All rights reserved.",
year = "2020",
month = oct,
doi = "10.1016/j.jpeds.2020.05.051",
language = "English",
volume = "225",
pages = "65--+",
journal = "The Journal of Pediatrics",
issn = "0022-3476",
publisher = "MOSBY-ELSEVIER",

}

RIS

TY - JOUR

T1 - The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension

AU - Haarman, Meindina G

AU - Kerstjens-Frederikse, Wilhelmina S

AU - Vissia-Kazemier, Theresia R

AU - Breeman, Karel T N

AU - Timens, Wim

AU - Vos, Yvonne J

AU - Roofthooft, Marc T R

AU - Hillege, Hans L

AU - Berger, Rolf M F

N1 - Copyright © 2020 Elsevier Inc. All rights reserved.

PY - 2020/10

Y1 - 2020/10

N2 - Objective To describe the prevalence of pulmonary arterial hypertension (PAH)-associated gene mutations, and other genetic characteristics in a national cohort of children with PAH from the Dutch National registry and to explore genotype-phenotype associations and outcomes.Study design Children (n = 70) diagnosed with idiopathic PAH, heritable PAH, PAH associated with congenital heart disease with coincidental shunt (PAH-congenital heart disease group 3), PAH after closure of a cardiac shunt (PAH-congenital heart disease group 4), or PAH associated with other noncardiac conditions were enrolled. Targeted next-generation sequencing was performed on PAH-associated genes (BMPR2, ACVRL1 , EIF2AK4, CAV1 , ENG, KCNK3, SMAD9, and TBX4). Also, children were tested for specific genetic disorders in case of clinical suspicion. Additionally, children were tested for copy number variations.Results Nineteen children (27%) had a PAH-associated gene mutation/variant: BMPR2 n = 7, TBX4 n = 8, ACVRL1 n = 1, KCNK3 n = 1, and EIF2AK4 n = 2. Twelve children (17%) had a genetic disorder with an established association with PAH (including trisomy 21 and cobalamin C deficiency). In another 16 children (23%), genetic disorders without an established association with PAH were identified (including Noonan syndrome, Beals syndrome, and various copy number variations). Survival rates differed between groups and was most favorable in TBX4 variant carriers.Conclusions Children with PAH show a high prevalence of genetic disorders, not restricted to established PAH-associated genes. Genetic architecture could play a role in risk-stratified care management in pediatric PAH.

AB - Objective To describe the prevalence of pulmonary arterial hypertension (PAH)-associated gene mutations, and other genetic characteristics in a national cohort of children with PAH from the Dutch National registry and to explore genotype-phenotype associations and outcomes.Study design Children (n = 70) diagnosed with idiopathic PAH, heritable PAH, PAH associated with congenital heart disease with coincidental shunt (PAH-congenital heart disease group 3), PAH after closure of a cardiac shunt (PAH-congenital heart disease group 4), or PAH associated with other noncardiac conditions were enrolled. Targeted next-generation sequencing was performed on PAH-associated genes (BMPR2, ACVRL1 , EIF2AK4, CAV1 , ENG, KCNK3, SMAD9, and TBX4). Also, children were tested for specific genetic disorders in case of clinical suspicion. Additionally, children were tested for copy number variations.Results Nineteen children (27%) had a PAH-associated gene mutation/variant: BMPR2 n = 7, TBX4 n = 8, ACVRL1 n = 1, KCNK3 n = 1, and EIF2AK4 n = 2. Twelve children (17%) had a genetic disorder with an established association with PAH (including trisomy 21 and cobalamin C deficiency). In another 16 children (23%), genetic disorders without an established association with PAH were identified (including Noonan syndrome, Beals syndrome, and various copy number variations). Survival rates differed between groups and was most favorable in TBX4 variant carriers.Conclusions Children with PAH show a high prevalence of genetic disorders, not restricted to established PAH-associated genes. Genetic architecture could play a role in risk-stratified care management in pediatric PAH.

KW - ACTA2 MUTATION

KW - BMPR2

KW - TBX4

KW - POLYCYTHEMIA

KW - ASSOCIATION

KW - GUIDELINES

KW - MANAGEMENT

KW - PHENOTYPE

KW - CONSENSUS

KW - VARIANTS

U2 - 10.1016/j.jpeds.2020.05.051

DO - 10.1016/j.jpeds.2020.05.051

M3 - Article

C2 - 32502478

VL - 225

SP - 65-+

JO - The Journal of Pediatrics

JF - The Journal of Pediatrics

SN - 0022-3476

ER -

ID: 126664716