Novel Compound Heterozygous ATAD3A Variants in Harel-Yoon Syndrome With Congenital Cataracts and Dilated Cardiomyopathy.

Authors

Tingting Wen, Hongyu Chen, Lan Yu, Xianghong Zhang

Published in

American journal of medical genetics. Part A. Oct 12, 2026. Epub Oct 12, 2026.

Abstract

Harel-Yoon syndrome is a rare mitochondrial disorder caused by pathogenic variants in ATAD3A, typically characterized by neonatal respiratory insufficiency, cataracts, developmental delay, hypotonia, and cerebellar atrophy. We report a pediatric patient with compound heterozygous missense variants in ATAD3A (c.655C>T, p.R219C and c.980G>C, p.R327P) who presented with an atypical phenotype manifested as early-onset congenital cataracts and progressive dilated cardiomyopathy. Notably the patient did not show typical neurological manifestations nor the cardiac presentations of hypertrophic cardiomyopathy. The maternally inherited c.655C>T variant was absent from population databases, while paternally inherited c.980G>C was previously associated with Harel-Yoon syndrome. In silico protein structure modeling demonstrated that the mutant ATAD3A hexamer showed a looser and more disorganized conformation compared to that of the wild-type, suggesting functional impairment. This case expands the phenotypic spectrum of ATAD3A-related disorders and highlights the importance of long-term surveillance in patients with ATAD3A variants, even in the absence of classical neurological features. In addition, our findings support the inclusion of ATAD3A in the genetic differential diagnosis for patients with congenital cataracts and cardiomyopathy.

PMID:
42864278
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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