Mitochondrial respiratory chain dysfunction in a patient with a heterozygous de novo CTBP1 variant
Wui‐Kwan Wong,
Shanti Balasubramaniam,
Rachel S. H. Wong,
Nicole Graf,
David R. Thorburn,
Robert McFarland,
Christopher Troedson
Affiliations
Wui‐Kwan Wong
TY Nelson Department of Neurology and Neurosurgery The Children's Hospital at Westmead Sydney New South Wales Australia
Shanti Balasubramaniam
Genetic Metabolic Disorders Service The Children's Hospital at Westmead Sydney New South Wales Australia
Rachel S. H. Wong
Genetic Metabolic Disorders Service The Children's Hospital at Westmead Sydney New South Wales Australia
Nicole Graf
Department of Histopathology The Children's Hospital at Westmead Sydney Australia
David R. Thorburn
Murdoch Children's Research Institute Melbourne Victoria Australia
Robert McFarland
Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University Newcastle upon Tyne UK
Christopher Troedson
TY Nelson Department of Neurology and Neurosurgery The Children's Hospital at Westmead Sydney New South Wales Australia
Abstract The C‐terminal binding protein 1 (CTBP1) functions as a transcriptional corepressor in vertebrates and has been identified to have critical roles in nervous system growth and development. Pathogenic variants in the CTBP1 gene has been shown to cause hypotonia, ataxia, developmental delay and tooth enamel defect syndrome (HADDTS). There have only been 16 cases reported to date with heterozygous, pathogenic variants in CTBP1 manifesting with a neurodevelopmental phenotype. We report a further case of a pathogenic, heterozygous, de novo variant in CTBP1 identified by whole exome sequencing in a female with the typical phenotype of global developmental delay, hypotonia, cerebellar dysfunction and failure to thrive. Additionally, muscle biopsy demonstrates evidence of a respiratory chain defect, only previously reported once in the literature. This supports the role of CTBP1 in maintenance of normal mitochondrial activity and highlights the importance of considering secondary mitochondrial dysfunction in genes not directly involved in the mitochondrial respiratory chain.
