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Case Reports
. 2025 May;197(5):e63994.
doi: 10.1002/ajmg.a.63994. Epub 2025 Jan 16.

Mitochondrial Complex I Deficiency: Unraveling the Relevance of NDUFAF1 in Pediatric Hypertrophic Cardiomyopathy

Silvia Kalantari  1   2 , Daniele Veraldi  3 , Davide Politano  4   5 , Antonia Apicella  3 , Riccardo Castagnoli  3   6 , Thomas Foiadelli  3 , Fulvio D'Abrusco  7 , Elisa Giorgio  1   8 , Angela Berardinelli  5 , Alessia Claudia Codazzi  3 , Gianluigi Marseglia  3   7 , Enza Maria Valente  1   8 , Fabio Sirchia  1   2
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Case Reports

Mitochondrial Complex I Deficiency: Unraveling the Relevance of NDUFAF1 in Pediatric Hypertrophic Cardiomyopathy

Silvia Kalantari et al. Am J Med Genet A. 2025 May.

Abstract

Hypertrophic cardiomyopathy (HCM) is rare in childhood, but it is associated with significant morbidity and mortality. Genetic causes of HCM are mostly related to sarcomeric genes abnormalities; however, syndromic, metabolic, and mitochondrial disorders play an important role in its etiopathogenesis in pediatric patients. We here describe a new case of apparently isolated HCM due to mitochondrial assembly factor gene NDUFAF1 biallelic variants (c.631C > T and an intragenic deletion encompassing exon 3, NM_016013.4). Alterations of this nuclear gene have been associated to Mitochondrial complex I deficiency, nuclear type 11 (OMIM *618234). We here report the fourth case of a child affected by complex I deficiency due to alterations in NDUFAF1 gene. His clinical features appear simpler when compared to the other cases described in the medical literature, increasing our knowledge regarding the highly heterogeneous clinical presentation associated with this disorder.

Keywords: NDUFAF1; hypertrophic cardiomiopathy; mitochondrial complex I deficiency.

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References

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