Expanding the Clinical Spectrum of Ndufb9 Variants: A Novel Case of Lvnc Publisher



R Abbaszadeh REZA ; M Arefzadeh MARYAM ; F Abedpour FATEMEH ; T Masoumi TANNAZ ; Z Hoseinkhani ZOHREH ; H Pouraliakbar HAMIDREZA ; F Emami FARNOOSH ; S Mirabsamiee SIAMAK ; N Mahdieh NEJAT
Source: Gene Reports Published:2025

Abstract

Background: Left ventricular non-compaction (LVNC) is a rare congenital cardiomyopathy often associated with genetic mutations that disrupt mitochondrial function. Here, we present the first case of LVNC linked to a missense variant in the NDUFB9 gene in an Iranian family. Materials and methods: The patient underwent clinical evaluation, including echocardiography, cardiac MRI, and genetic testing. Given the limited number of published cases regarding NDUFB9 variants, a comprehensive case report is presented here, integrating relevant literature for comparison. Results: The patient, a 2-month-old infant, presented with classic symptoms of mitochondrial complex I deficiency, such as fatigue during feeding, palpitations, and excessive sweating. LVNC with marked left ventricular trabeculation and enlargement was confirmed. A novel homozygous NDUFB9 c.283G>A variant was identified and predicted to impair mitochondrial complex I activity. Four additional studies were found to report NDUFB9 variants, with clinical manifestations including mitochondrial encephalopathies, cardiomyopathy, and leukodystrophy. Conclusion: This report links the NDUFB9 gene with LVNC, broadening the clinical spectrum of NDUFB9-related disorders. These findings highlight the significant role of mitochondrial dysfunction in the pathogenesis of LVNC and emphasize the need for genetic screening in patients with congenital cardiomyopathies. Further research is required to assess the prevalence and mechanisms of NDUFB9 variants across diverse populations. © 2025 Elsevier B.V., All rights reserved.