ArticleAmerican journal of human genetics2020
Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- ATAD3B and SKIL polymorphisms associated with antipsychotic-induced QTc interval change in patients with schizophrenia: a genome-wide association study.Translational psychiatry · 2022Trial
- Structural Variation and Its Roles in Plant Genomes.Plants (Basel, Switzerland) · 2026Review
- Computational strategies for copy number variation detection, disease association, and beyond.Genome biology · 2026Review
- Cholesterol in Mitochondrial Diseases-Friend or Foe?International journal of molecular sciences · 2026Review
- Comprehensive Clinical, Diagnostic, and In Silico Assessment of a Novel 1p36.33p36.32 Copy Number Variant.Journal of cellular and molecular medicine · 2026Article
- ATAD3 duplications bridge mitochondrial diseases and Aicardi-Goutières syndrome.Developmental medicine and child neurology · 2026Article
- [A case of Harel-Yoon syndrome with seizures caused by anZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Safe General Anesthesia in a Pediatric Patient With 1p36.33 Duplication Syndrome: A Rare Case Report.Clinical case reports · 2025Article
- Clinical and variant spectrum of patients harboringTranslational pediatrics · 2025Article
- Diversity and consequences of structural variation in the human genome.Nature reviews. Genetics · 2025Review
- Clinical characteristics and induced pluripotent stem cells (iPSCs) disease model of Harel-Yoon syndrome caused by compound heterozygous ATAD3A variants.Human cell · 2025Article
- Transcriptome analysis of atad3-null zebrafish embryos elucidates possible disease mechanisms.Orphanet journal of rare diseases · 2025Article
- Elevated cholesterol is a common phenotype for dominant and recessive ATAD3-associated disorders.Brain : a journal of neurology · 2025Article
- Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation.Brain : a journal of neurology · 2024Article
- Mutations in mitochondrialFrontiers in neuroscience · 2024Review
- Article
- ATAD3A: A Key Regulator of Mitochondria-Associated Diseases.International journal of molecular sciences · 2023Review
- ATAD3A-related pontocerebellar hypoplasia: new patients and insights into phenotypic variability.Orphanet journal of rare diseases · 2023Article
- Mitochondrial biology and dysfunction in secondary mitochondrial disease.Open biology · 2022Review
- Severe spinal cord hypoplasia due to a novelMolecular genetics and metabolism reports · 2022Article
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Authors and funding
29 authors at 16 institutions in 4 countries.
Funding
Abstract
Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data.
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