Dataset Information

Damaging Variants in Proangiogenic Genes Impair Growth in Fetuses with Cardiac Defects.

ABSTRACT: OBJECTIVE:To determine the impact of damaging genetic variation in proangiogenic pathways on placental function, complications of pregnancy, fetal growth, and clinical outcomes in pregnancies with fetal congenital heart defect. STUDY DESIGN:Families delivering a baby with a congenital heart defect requiring surgical repair in infancy were recruited. The placenta and neonate were weighed and measured. Hemodynamic variables were recorded from a third trimester (36.4 ± 1.7 weeks) fetal echocardiogram. Exome sequencing was performed on the probands (N = 133) and consented parents (114 parent-child trios, and 15 parent-child duos) and the GeneVetter analysis tool used to identify damaging coding sequence variants in 163 genes associated with the positive regulation of angiogenesis (PRA) (GO:0045766). RESULTS:In total, 117 damaging variants were identified in PRA genes in 133 congenital heart defect probands with 73 subjects having at least 1 variant. Presence of a damaging PRA variant was associated with increased umbilical artery pulsatility index (mean 1.11 with variant vs 1.00 without; P = .01). The presence of a damaging PRA variant was also associated with lower neonatal length and head circumference for age z score at birth (mean -0.44 and -0.47 with variant vs 0.23 and -0.05 without; P = .01 and .04, respectively). During median 3.1 years (IQR 2.0-4.1 years) of follow-up, deaths occurred in 2 of 60 (3.3%) subjects with no PRA variant and in 9 of 73 (12.3%) subjects with 1 or more PRA variants (P = .06). CONCLUSIONS:Damaging variants in proangiogenic genes may impact placental function and are associated with impaired fetal growth in pregnancies involving a fetus with congenital heart defect.

SUBMITTER: Russell MW

PROVIDER: S-EPMC6765419 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Damaging Variants in Proangiogenic Genes Impair Growth in Fetuses with Cardiac Defects.

Russell Mark W MW Moldenhauer Julie S JS Rychik Jack J Burnham Nancy B NB Zullo Erin E Parry Samuel I SI Simmons Rebecca A RA Elovitz Michal A MA Nicolson Susan C SC Linn Rebecca L RL Johnson Mark P MP Yu Sunkyung S Sampson Matthew G MG Hakonarson Hakon H Gaynor J William JW

The Journal of pediatrics 20190618

<h4>Objective</h4>To determine the impact of damaging genetic variation in proangiogenic pathways on placental function, complications of pregnancy, fetal growth, and clinical outcomes in pregnancies with fetal congenital heart defect.<h4>Study design</h4>Families delivering a baby with a congenital heart defect requiring surgical repair in infancy were recruited. The placenta and neonate were weighed and measured. Hemodynamic variables were recorded from a third trimester (36.4 ± 1.7 weeks) fet ...[more]

PMID: 31227283

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Dataset Information

Damaging Variants in Proangiogenic Genes Impair Growth in Fetuses with Cardiac Defects.

Publications

Damaging Variants in Proangiogenic Genes Impair Growth in Fetuses with Cardiac Defects.

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