A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus

Ke, Zun‐Ping; Zhang, Gaofeng; Guo, Yu-Han; Sun, Yu-Min; Wang, Jun; Li, Ning; Qiu, Xing‐Biao; Xu, Ying‐Jia; Yang, Yi‐Qing

doi:10.1590/1678-4685-gmb-2021-0378

Cited by 11 publications

(5 citation statements)

References 71 publications

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“…In addition, Ke et al reported a family with a PRRX1 heterozygous mutation that resulted in familial PDA and atrial fibrillation caused by PRRX1 loss of function. The family is at a significantly increased risk of stroke ( 99 ). In conclusion, the relationship between VSD and PDA and brain diseases is still unclear, but it should be considered in clinical practice that VSD and PDA may be the etiology or risk factors for some difficult neuropsychiatric cases.…”

Section: Left-to-right Shunt and Brain Diseasesmentioning

confidence: 99%

Heart-brain axis: Association of congenital heart abnormality and brain diseases

Sha

Li²,

Zhang³

et al. 2023

Front. Cardiovasc. Med.

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Brain diseases are a major burden on human health worldwide, and little is known about how most brain diseases develop. It is believed that cardiovascular diseases can affect the function of the brain, and many brain diseases are associated with heart dysfunction, which is called the heart-brain axis. Congenital heart abnormalities with anomalous hemodynamics are common treatable cardiovascular diseases. With the development of cardiovascular surgeries and interventions, the long-term survival of patients with congenital heart abnormalities continues to improve. However, physicians have reported that patients with congenital heart abnormalities have an increased risk of brain diseases in adulthood. To understand the complex association between congenital heart abnormalities and brain diseases, the paper reviews relevant clinical literature. Studies have shown that congenital heart abnormalities are associated with most brain diseases, including stroke, migraine, dementia, infection of the central nervous system, epilepsy, white matter lesions, and affective disorders. However, whether surgeries or other interventions could benefit patients with congenital heart abnormalities and brain diseases remains unclear because of limited evidence.

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Section: Left-to-right Shunt and Brain Diseasesmentioning

confidence: 99%

Heart-brain axis: Association of congenital heart abnormality and brain diseases

Sha

Li²,

Zhang³

et al. 2023

Front. Cardiovasc. Med.

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“…This leads to increased myocardial contractility and heart rate, which can cause left congestive heart failure, which can progress to pulmonary edema, atrial fibrillation, moderate pulmonary hypertension secondary to left congestive heart failure and mitral regurgitation secondary to left ventricular dilation. [4][5][6]…”

Section: Introductionmentioning

confidence: 99%

A case report of patent ductus arteriosus in a Brazilian longhair female kitten

Ruggero Errante

2024

JDVAR

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Among the congenital cardiac alterations observed in small pets, the persistence of the right aortic arch has been described as a rare anomaly in cats. The ductus arteriosus corresponds to a normal fetal vascular structure derived from the distal portion of the sixth left aortic arch that connects the pulmonary artery to the dorsal aorta. During fetal life, this structure has the function of transporting oxygenated blood from the maternal placenta to the aorta, bypassing the collapsed lungs of the fetus. At birth, the increase of O2 partial pressure dissolved in arterial blood (PaO2) and the decline in prostaglandin concentration cause the closure of the ductus arteriosus in the first hours of life, giving rise to the ligamentum arteriosus. If this process does not occur, the ductus arteriosus will remain patent. In this case report, a 4-month-old longhair female kitten was treated, and, during auscultation, a heart murmur was found. After performing a Doppler echocardiogram and color flow mapping, the presence of continuous turbulent flow in the pulmonary artery was demonstrated, characteristic of patent ductus arteriosus persistence. The animal was sent for surgery, and in the post-surgical Doppler echocardiogram, correction of patent ductus arteriosus was verified, demonstrating the absence of continuous turbulent flow in the pulmonary artery.

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“…Genetic defects responsible for CHD include aneuploidy (presence of an additional chromosome, absence of a chromosome, or deletion/duplication of one arm of a chromosome), copy number variation (deletion or duplication of a segment of a chromosome), and genetic mutations [ 44 , 45 , 46 ]. To date, pathogenic mutations in over 100 genes have been involved in the occurrence of CHD, of which most encode cardiac transcription factors, cell adhesion molecules, signaling pathway proteins, and cardiac structural proteins essential for cardiovascular morphogenesis [ 44 , 45 , 46 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. However, CHD is of pronounced genetic heterogeneity, and the genetic determinants causative for CHD in a significant proportion of cases remain to be identified.…”

Section: Introductionmentioning

confidence: 99%

Discovery of GJC1 (Cx45) as a New Gene Underlying Congenital Heart Disease and Arrhythmias

Wang

et al. 2023

Biology

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As the most prevalent type of birth malformation, congenital heart disease (CHD) gives rise to substantial mortality and morbidity as well as a socioeconomic burden. Although aggregating investigations highlight the genetic basis for CHD, the genetic determinants underpinning CHD remain largely obscure. In this research, a Chinese family suffering from autosomal dominant CHD (atrial septal defect) and arrhythmias was enrolled. A genome-wide genotyping with microsatellite markers followed by linkage assay as well as sequencing analysis was conducted. The functional effects of the discovered genetic mutation were characterized by dual patch-clamp electrophysiological recordings in N2A cells and propidium iodide uptake assays in HeLa cells. As a result, a novel genetic locus for CHD and arrhythmias was located on chromosome 17q21.31-q21.33, a 4.82-cM (5.12 Mb) region between two markers of D17S1861 and D17S1795. Sequencing assays of the genes at the mapped locus unveiled a novel heterozygous mutation in the GJC1 gene coding for connexin 45 (Cx45), NM_005497.4:c.550A>G;p.R184G, which was in co-segregation with the disease in the whole family and was not observed in 516 unrelated healthy individuals or gnomAD. Electrophysiological analyses revealed that the mutation significantly diminished the coupling conductance in homomeric cell pairs (R184G/R184G) and in cell pairs expressing either R184G/Cx45 or R184G/Cx43. Propidium iodide uptake experiments demonstrated that the Cx45 R184G mutation did not increase the Cx45 hemichannel function. This investigation locates a new genetic locus linked to CHD and arrhythmias on chromosome 17q21.31-q21.33 and indicates GJC1 as a novel gene predisposing to CHD and arrhythmias, implying clinical implications for prognostic risk assessment and personalized management of patients affected with CHD and arrhythmias.

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A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus

Cited by 11 publications

References 71 publications

Heart-brain axis: Association of congenital heart abnormality and brain diseases

Heart-brain axis: Association of congenital heart abnormality and brain diseases

A case report of patent ductus arteriosus in a Brazilian longhair female kitten

Discovery of GJC1 (Cx45) as a New Gene Underlying Congenital Heart Disease and Arrhythmias

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