Human Genetics of Ventricular Septal Defect

Bellmann, Katherina; Perrot, Andreas; Rickert-Sperling, Silke

doi:10.1007/978-3-7091-1883-2_23

Cited by 7 publications

(5 citation statements)

References 109 publications

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“…Dozens of genetic mutations are known to cause muscular VSDs, but how the heart defect forms is poorly understood 29 30 . A novel genetic interaction between Nkx2-5 and Sspn offers insight into the mechanism.…”

Section: Discussionmentioning

confidence: 99%

Nkx2-5 and Sarcospan genetically interact in the development of the muscular ventricular septum of the heart

Panzer

Regmi

Cormier

et al. 2017

Sci Rep

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The muscular ventricular septum separates the flow of oxygenated and de-oxygenated blood in air-breathing vertebrates. Defects within it, termed muscular ventricular septal defects (VSDs), are common, yet less is known about how they arise than rarer heart defects. Mutations of the cardiac transcription factor NKX2-5 cause cardiac malformations, including muscular VSDs. We describe here a genetic interaction between Nkx2-5 and Sarcospan (Sspn) that affects the risk of muscular VSD in mice. Sspn encodes a protein in the dystrophin-glycoprotein complex. Sspn knockout (SspnKO) mice do not have heart defects, but Nkx2-5+/−/SspnKO mutants have a higher incidence of muscular VSD than Nkx2-5+/− mice. Myofibers in the ventricular septum follow a stereotypical pattern that is disrupted around a muscular VSD. Subendocardial myofibers normally run in parallel along the left ventricular outflow tract, but in the Nkx2-5+/−/SspnKO mutant they commonly deviate into the septum even in the absence of a muscular VSD. Thus, Nkx2-5 and Sspn act in a pathway that affects the alignment of myofibers during the development of the ventricular septum. The malalignment may be a consequence of a defect in the coalescence of trabeculae into the developing ventricular septum, which has been hypothesized to be the mechanistic basis of muscular VSDs.

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Section: Discussionmentioning

confidence: 99%

Nkx2-5 and Sarcospan genetically interact in the development of the muscular ventricular septum of the heart

Panzer

Regmi

Cormier

et al. 2017

Sci Rep

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“…33 In humans, VSDs have similarly been found to have a genetic cause, with both recessive and dominant modes of inheritance found in different familial cases. 35 The genes most often involved are the T-box transcription factor (TBX5) and GATA4, which are embryologic cardiac development genes encoding transcription factors and/or signalling molecules. 35 Similar mechanisms may exist for VSDs in Arabian horses, with further research required to investigate candidate variants.…”

Section: Ventricular Septal Defectmentioning

confidence: 99%

“…35 The genes most often involved are the T-box transcription factor (TBX5) and GATA4, which are embryologic cardiac development genes encoding transcription factors and/or signalling molecules. 35 Similar mechanisms may exist for VSDs in Arabian horses, with further research required to investigate candidate variants.…”

Section: Ventricular Septal Defectmentioning

confidence: 99%

Congenital heart defects in Arabian horses and the prospects of genetic testing: A review

Brown,

Stefaniuk‐Szmukier,

Decloedt

et al. 2024

Equine Veterinary Journal

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Congenital heart defects (CHDs) can have profound and potentially life‐threatening consequences on horses' health and performance capability. While CHDs are rare in the general horse population, the Arabian breed is disproportionately overrepresented and thus is widely suspected to be genetically predisposed. This review discusses the most common CHDs in Arabian horses, including ventricular septal defect (VSD), tetralogy of Fallot (TOF), patent duct arteriosus (PDA), tricuspid valve atresia (TVA) and atrial septal defect (ASD). This review also explores how future research into the genetic factors that likely underpin many CHDs can revolutionise the way these disorders are managed in Arabian horses.

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“…The complex genetic control of heart development is a major factor for heterogeneous VSDs. Numerous polymorphisms and mutations of many genes (encoding for transcriptional factors, signal transduction pathway components, and structural heart proteins) involved in cardiac development are known to increase the risk factor of VSDs [6].…”

Section: Introductionmentioning

confidence: 99%

Hematological and demographic profile of Pakistani children with isolated ventricular septal defects (VSDs)

Sarwar

Shabana

Ehsan

et al. 2020

Egypt J Med Hum Genet

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Background Cardiac morphogenesis is a dynamic and complex process that involves a complex interaction of many genetic and environmental factors. Ventricular septal defects (VSDs) are the commonest congenital heart defects (CHDs), accounting for ~ 40% of all cardiac malformations. In Pakistan, the prevalence of VSD is increasing (4–6 in 1000 live births). In the current study, we aimed to determine the pattern of different hematological parameters and various risk factors in VSDs in local pediatric patients. We recruited the clinically diagnosed VSD children (n = 125) from various hospitals. The diagnosis was made based on echocardiography, size, number, and exact location of the defect. Hematological parameters, chemical pathological assays, and liver function analysis were performed. The blood group distribution and various risk factors were also assessed. The statistical analysis was done using the SPSS (IBM statistics version 22) software. Results The results showed that for RBCs, 20% of patients in category of 0 to 3 months are above normal range; for WBCs, 33.3% of patients are above normal range in category of 4–5 years and 12–14 years. For hemoglobin, highest percentage of patients was observed below normal range; 30% of patients in category of 0 to 3 months, 40% of patients in category 4–9 months, 35.2% of patients in category of 10 months–3 years, and 33.3% of patients in category of 12–14 years were below normal range. For platelet count, 5.66% patients were below normal range and 16.9% were above normal range. For prothrombin time (PT) and activated partial thromboplastin time (APTT) more than 90% patients were in normal range value. Elevated ALP level and significantly lower albumin levels were observed. In age range of 13–14 years, 50% patients were below range for both calcium and serum creatinine. The prevalence of cousin marriages was 62.3%, about 60% mothers used antibiotics during pregnancy, B + ve and O + ve had the highest frequencies, and most of the patients were seen in age group of 2–35 months. Conclusion All tested parameters show divergence from normal values their predictive capabilities of VSDs. To the best of our knowledge, the present study is the first to report data on hematological parameters and demographic risk factor associated with VSDs, in the Pakistani children. This data may have implication on the characterization and diagnosis of VSDs as well as on the assessment of related risk factors.

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Human Genetics of Ventricular Septal Defect

Cited by 7 publications

References 109 publications

Nkx2-5 and Sarcospan genetically interact in the development of the muscular ventricular septum of the heart

Nkx2-5 and Sarcospan genetically interact in the development of the muscular ventricular septum of the heart

Congenital heart defects in Arabian horses and the prospects of genetic testing: A review

Hematological and demographic profile of Pakistani children with isolated ventricular septal defects (VSDs)

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