Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism

• Published in: American journal of human genetics Vol. 106; no. 2; pp. 272 - 279
• Main Authors: Gunning, Adam C., Strucinska, Klaudia, Muñoz Oreja, Mikel, Parrish, Andrew, Caswell, Richard, Stals, Karen L., Durigon, Romina, Durlacher-Betzer, Karina, Cunningham, Mitchell H., Grochowski, Christopher M., Baptista, Julia, Tysoe, Carolyn, Baple, Emma, Lahiri, Nayana, Homfray, Tessa, Scurr, Ingrid, Armstrong, Catherine, Dean, John, Fernandez Pelayo, Uxoa, Jones, Aleck W.E., Taylor, Robert W., Misra, Vinod K., Yoon, Wan Hee, Wright, Caroline F., Lupski, James R., Spinazzola, Antonella, Harel, Tamar, Holt, Ian J., Ellard, Sian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.02.2020; Elsevier
• Subjects: Amino Acid Sequence; ATAD3; ATAD3 gene cluster; ATPases Associated with Diverse Cellular Activities - chemistry; ATPases Associated with Diverse Cellular Activities - genetics; Brain Diseases - etiology; Brain Diseases - metabolism; Brain Diseases - pathology; Cardiomyopathies - etiology; Cardiomyopathies - metabolism; Cardiomyopathies - pathology; cardiomyopathy; cholesterol; Cholesterol - metabolism; Corneal Opacity - etiology; Corneal Opacity - metabolism; Corneal Opacity - pathology; DNA Copy Number Variations; Female; Gene Duplication; Gene Rearrangement; Harel-Yoon; Homologous Recombination; Humans; Infant; Infant, Newborn; Male; Membrane Proteins - chemistry; Membrane Proteins - genetics; metabolic disorder; Mitochondria - genetics; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial Diseases - genetics; Mitochondrial Diseases - metabolism; Mitochondrial Diseases - pathology; mitochondrial DNA; Mitochondrial Proteins - chemistry; Mitochondrial Proteins - genetics; Muscle Hypotonia - etiology; Muscle Hypotonia - metabolism; Muscle Hypotonia - pathology; Mutation; NAHR; non-allelic homologous recombination; Protein Conformation; Seizures - etiology; Seizures - metabolism; Seizures - pathology; Sequence Homology; Harel-Yoon; non-allelic homologous recombination; mitochondrial DNA; ATAD3; metabolic disorder; cholesterol; ATAD3 gene cluster; NAHR; cardiomyopathy

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 disord...