| Revue: | Genetics and molecular biology |
| Base de datos: | PERIÓDICA |
| Número de sistema: | 000459240 |
| ISSN: | 1415-4757 |
| Autores: | Ke, Zun-Ping1 Zhang, Gao-Feng1 Guo, Yu-Han1 Sun, Yu-Min2 Wang, Jun2 Li, Ning3 Qiu, Xing-Biao3 Xu, Ying-Jia1 Yang, Yi-Qing1 |
| Instituciones: | 1Fudan University, Shanghai Fifth People’s Hospital, Shanghai. China 2Fudan University, Shanghai Jing'an District Central Hospital, Shanghai, Shanghai. China 3Shanghai Jiao Tong University, Shanghai Chest Hospital, Shanghai. China |
| Año: | 2022 |
| Volumen: | 45 |
| Número: | 2 |
| País: | Brasil |
| Idioma: | Inglés |
| Tipo de documento: | Artículo |
| Enfoque: | Experimental, analítico |
| Resumen en inglés | Atrial fibrillation (AF) represents the most common type of sustained cardiac arrhythmia in humans and confers a significantly increased risk for thromboembolic stroke, congestive heart failure and premature death. Aggregating evidence emphasizes the predominant genetic defects underpinning AF and an increasing number of deleterious variations in more than 50 genes have been involved in the pathogenesis of AF. Nevertheless, the genetic basis underlying AF remains incompletely understood. In the current research, by whole-exome sequencing and Sanger sequencing analysis in a family with autosomal-dominant AF and congenital patent ductus arteriosus (PDA), a novel heterozygous variation in the PRRX1 gene encoding a homeobox transcription factor critical for cardiovascular development, NM_022716.4:c.373G>T;p.(Glu125*), was identified to be in co-segregation with AF and PDA in the whole family. The truncating variation was not detected in 306 unrelated healthy individuals employed as controls. Quantitative biological measurements with a reporter gene analysis system revealed that the Glu125*-mutant PRRX1 protein failed to transactivate its downstream target genes SHOX2 and ISL1, two genes that have been causally linked to AF. Conclusively, the present study firstly links PRRX1 loss-of-function variation to AF and PDA, suggesting that AF and PDA share a common abnormal developmental basis in a proportion of cases |
| Disciplinas: | Medicina |
| Palabras clave: | Sistema cardiovascular, Medicina general y familiar, Arritmia cardiaca, Defectos cardiacos congénitos |
| Keyword: | PRRX1, Cardiovascular system, General practice and family health, Cardiac arrhythmia, Congenital heart defect, PRRX1 |
| Texte intégral: | Texto completo (Ver HTML) Texto completo (Ver PDF) |
