Work

Case Report: Newly discovered ELN gene mutation in congenital heart disease: case analysis and review

Year: 2026

Type: article

Abstract: Introduction: Supravalvular aortic stenosis (SVAS) is a rare left ventricular outflow tract obstruction, most commonly caused by pathogenic variants in ELN. Truncating variants in exons 1-29 typically produce non-syndromic SVAS through elastin haploinsufficiency, whereas C-terminal variants are linked to autosomal dominant cutis laxa. However, clinically and mechanistically well-characterized variants in the distal part of this "stenotic zone," such as exon 28, remain uncommon. Methods: We conducted a retrospective family-based case report with standardized clinical evaluation, serial echocardiography, and trio whole-exome sequencing with Sanger confirmation and conservation analysis. Results: A female infant presented at 1 month with severe sinotubular junction narrowing (Z-score -4.8, peak gradient 24 mmHg), severe peripheral pulmonary artery stenosis, a small atrial septal defect, and moderate mitral regurgitation. Her father had severe SVAS with mild PPAS and prior aortic root enlargement, without syndromic features. Trio sequencing identified a novel heterozygous ELN exon 28 frameshift variant, c.1879_1883dup (p.Ala629LeufsTer15), inherited from the father. Ala629 is fully conserved, and the duplication introduces a premature stop codon, consistent with nonsense-mediated decay and elastin haploinsufficiency. At 9 months, SVAS progressed (peak gradient 35 mmHg), while PPAS gradients regressed by >40%. Conclusion: This novel exon 28 ELN frameshift expands the non-syndromic SVAS spectrum and illustrates a characteristic pattern of progressive aortic stenosis with improving PPAS, supporting ELN testing and targeted longitudinal surveillance in similar patients and families.

Source: Frontiers in Pediatrics

DOI: 10.3389/fped.2026.1671066

Authors: Peiwen Cheng, Guozhen Wang, Jialin Qiu, Xia Xie, Yong An

Institutions: Children's Hospital of Chongqing Medical University, Chongqing Medical University

Language: English

Topic: Connective tissue disorders research

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801