Genetic and genomics in congenital heart disease: a clinical review

Saliba, Aline; Figueiredo, Ana Carolina Vaqueiro; Baroneza, José Eduardo; Afiune, Jorge Yussef; Pic‐Taylor, Aline; Oliveira, Silviene Fabiana de; Mazzeu, Juliana Forte

doi:10.1016/j.jpedp.2019.07.002

Cited by 8 publications

(7 citation statements)

References 44 publications

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“…This syndrome is associated with heterogeneous clinical pictures, even within the same family. Generally, patients present alterations such as immunodeficiency, hypocalcemia, hypoparathyroidism, characteristically abnormal facial features, impaired neurological development and cardiac malformations [ 105 ]. The latter can be identified in up to 70% of cases, and consist mainly of cono-truncal development impairment such as anomalies of the aortic arch (right aortic arch, double or interrupted type B aortic arch), misaligned VSD, HLHS, TGV, ASD, pulmonary atresia or PS, ToF, and CTA ( Table 1 ).…”

Section: Syndromes With Congenital Cardiac Alterationmentioning

confidence: 99%

Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Diz

Toro

César

et al. 2021

JPM

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Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach.

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Section: Syndromes With Congenital Cardiac Alterationmentioning

confidence: 99%

Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Diz

Toro

César

et al. 2021

JPM

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“…No tocante ao tratamento da cardiopatia, este dependerá do tipo e da gravidade, em cardiopatias leves há elevada possibilidade de cura sem intervenção medicamentosa ou cirúrgica. Em outros casos podem ser necessários tratamentos medicamentosos ou cirurgia cardíaca (15,16) .…”

Section: Discussionunclassified

Caracterização de crianças com cardiopatias congênitas em um hospital no estado da Paraíba

Silva¹,

Vieira²,

Souza³

et al. 2020

SaudColetiv (Barueri)

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Caracterizar o perfil clínico epidemiológico e verificar a correlação entre idade e tempo de internação de crianças com cardiopatias congênitas. Trata-se de um estudo transversal com abordagem quantitativa baseada na análise de prontuários de crianças admitidas com diagnóstico de cardiopatia congênita. A amostra foi composta por 66 prontuários. A faixa etária predominante foi a de lactentes com 54,5%; 45,5% apresentaram peso entre 3.500 kg a 10 kg; e o comprimento de 57% da amostra encontrava-se entre 55 a 86 cm. Houve a identificação de um estado afebril em 98,5%, a frequência cardíaca em 87,7% era maior que 100 batimentos por minuto, a frequência respiratória em 92,3% era igual ou menor que 60 incursões respiratórias por minuto, e a saturação em 78,5% dos casos era igual ou maior que 91%. As cardiopatias congênitas acianóticas foram mais prevalentes. O estudo proporcionou a reflexão sobre as dificuldades na identificação das cardiopatias congênitas acianóticas.

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“…In vertebrates, the heart is the first functional organ that develops during embryonic morphogenesis, and cardiac organogenesis undergoes an extremely complex biological process, which is precisely mediated by a sophisticated regulatory network, involving transcription factors, cardiac structural proteins, signaling transducers, epigenetic modifiers and microRNAs (48). Previous studies have demonstrated that both environmental risk factors and genetic defects may interfere with this finely controlled developmental process, giving rise to CHD (1,2,(48)(49)(50)(51)(52)(53)(54). The well-recognized non-inheritable pathogenic factors for CHD include maternal viral infection, nutritional deficiency, obesity, diabetes and decreased physical activity, as well as exposure to toxic chemicals, therapeutic drugs and ionizing radiation during early pregnancy (48)(49)(50)(51).…”

Section: Introductionmentioning

confidence: 99%

“…Significant familial aggregation of CHD has been reported, with the risk of CHD recurrence in the first-degree offspring of an affected parent being between 3 and 19% depending on the distinct types of lesion (55). In addition to chromosomal alterations encompassing aneuploidies, microdeletions and microduplications, pathogenetic variations in >100 genes amply expressed in the developing heart, encompassing those encoding sarcomeric proteins, transcription factors, chromatin modifies and signal-transducing molecules, have been determined to contribute to CHD (1,2,52,53,. Of these reported CHD-causative genes, the majority code for cardiac core transcription factors, such as T-box transcription factor (TBX)1, TBX20, TBX5, NK2 homeobox 5, GATA binding protein (GATA)6, GATA4, GATA5, heart and neural crest derivatives expressed (HAND)1 and HAND2 (84).…”

Section: Introductionmentioning

confidence: 99%

A novel KLF13 mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve

et al. 2022

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Recently, mutations in the Kruppel-like factor 13 (KLF13) gene encoding a Kruppel-like transcription factor have been reported to cause congenital heart disease (CHD). However, due to pronounced genetic heterogeneity, the mutational spectrum of KLF13 in other cohorts of cases suffering from distinct types of CHD remain to be ascertained. In the present investigation, by Sanger sequencing of KLF13 in 316 unrelated cases affected by different forms of CHD, a new mutation in heterozygous status, NM_015995.3: c.430G>T; p.(Glu144*), was detected in an index patient affected with patent ductus arteriosus (PDA) and ventricular septal defect (VSD), as well as bicuspid aortic valve (BAV), with a mutation frequency of ~0.32%. Genetic investigation of the available family members of the proband demonstrated that the truncating mutation co-segregated with CHD. The nonsense mutation was not observed in 400 unrelated volunteers without CHD who were enrolled as control subjects. Quantitative biological measurements with dual luciferase reporters revealed that Glu144*-mutant KLF13 did not transactivate the downstream genes vascular endothelial growth factor A and natriuretic peptide A. In addition, the mutation abrogated the synergistic transcriptional activation between KLF13 and T-box transcription factor 5, a well-established CHD-causing gene. In conclusion, the present study indicates that genetically defective KLF13 contributes to familial PDA and VSD, as well as BAV, which expands the phenotypic spectrum linked to KLF13, and reveals a novel molecular pathogenesis of the disease, providing a new molecular target for the early prophylaxis and individualized treatment of CHD.

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Genetic and genomics in congenital heart disease: a clinical review

Cited by 8 publications

References 44 publications

Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Caracterização de crianças com cardiopatias congênitas em um hospital no estado da Paraíba

A novel KLF13 mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve

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Genetic and genomics in congenital heart disease: a clinical review

Cited by 8 publications

References 44 publications

Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Caracterização de crianças com cardiopatias congênitas em um hospital no estado da Paraí­ba

A novel KLF13 mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve

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Caracterização de crianças com cardiopatias congênitas em um hospital no estado da Paraíba