CASE REPORT article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1663959
This article is part of the Research TopicNew Insights in Rare Genes Involved in Inherited Cardiac DiseasesView all articles
A novel missense variant of FGD5 in a family with Tetralogy of Fallot
Provisionally accepted
- 1Central South University, Changsha, China
- 2Xinjiang Medical University, Urumqi, China
- 3Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, China
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Background: Congenital heart disease (CHD) is among the most prevalent birth defects in newborns, with Tetralogy of Fallot (TOF) a classic example. Within weeks to months after birth, infants with TOF often exhibit cyanosis of the skin, lips, or nails and respiratory distress. Early medical intervention is crucial to enhance outcomes and ensure a better long-term prognosis. Methods and Results: A young Chinese couple were referred for prenatal counseling at gestational age 26+3 weeks for fetal complex CHD, pulmonary artery stenosis, widened aorta with overriding, and absence of ductus arteriosus in their affected fetus, who was later diagnosed with TOF. To determine the genetic basis of the congenital heart defect, whole-exome sequencing and Sanger sequencing was performed to identify potential pathogenic variants. Subsequently, a heterozygous missense variant (c. 3233C>A, p. T1078K) of FGD5 was identified in both the affected fetus and its unaffected carrier mother, demonstrating an inheritance pattern with irregular dominance. This variant is exceptionally rare in public genomic databases, was the genetic cause of TOF in the proband. Conclusion: We identified a novel heterozygous missense variant of FGD5 in a Chinese family with TOF, which enlarges the genetic spectrum of the disease.
Keywords: Tetralogy of Fallot, FGD5, Genetic variant, Whole-exome sequencing, irregular dominance
Received: 11 Jul 2025; Accepted: 19 Sep 2025.
Copyright: © 2025 Xiang, Liu, Dong and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rong Xiang, shirlesmile@csu.edu.cn
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