Whole exome sequencing reveals a homozygous C1QBP deletion as the cause of progressive external ophthalmoplegia and multiple mtDNA deletions

Case Reports

. 2021 Jul 4;S0960-8966(21)00176-0.

doi: 10.1016/j.nmd.2021.06.014.

Online ahead of print.

Affiliations

¹ School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands; Department of Toxicogenomics, Clinical Genomics Unit, Maastricht University, Maastricht, the Netherlands.
² Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Center for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India.
³ School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands.
⁴ Maastricht Center for Systems Biology (MacsBio), Maastricht University, Maastricht, the Netherlands.
⁵ Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands.
⁶ Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
⁷ Neuromuscular Laboratory, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
⁸ The Faculty of Medicine and Health, The Children’s Hospital at Westmead Clinical School, Sydney Medical School, The University of Sydney, NSW, Australia.
⁹ School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands; Department of Toxicogenomics, Clinical Genomics Unit, Maastricht University, Maastricht, the Netherlands; School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, the Netherlands. Electronic address: bert.smeets@maastrichtuniversity.nl.

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Case Reports

Le Guo et al.

Neuromuscul Disord.

2021.

. 2021 Jul 4;S0960-8966(21)00176-0.

doi: 10.1016/j.nmd.2021.06.014.

Online ahead of print.

Affiliations

¹ School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands; Department of Toxicogenomics, Clinical Genomics Unit, Maastricht University, Maastricht, the Netherlands.
² Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Center for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India.
³ School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands.
⁴ Maastricht Center for Systems Biology (MacsBio), Maastricht University, Maastricht, the Netherlands.
⁵ Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands.
⁶ Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
⁷ Neuromuscular Laboratory, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
⁸ The Faculty of Medicine and Health, The Children’s Hospital at Westmead Clinical School, Sydney Medical School, The University of Sydney, NSW, Australia.
⁹ School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands; Department of Toxicogenomics, Clinical Genomics Unit, Maastricht University, Maastricht, the Netherlands; School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, the Netherlands. Electronic address: bert.smeets@maastrichtuniversity.nl.

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Abstract

Whole exome sequencing (WES), analyzed with GENESIS and WeGET, revealed a homozygous deletion in the C1QBP gene in a patient with progressive external ophthalmoplegia (PEO) and multiple mtDNA deletions. The gene encodes the mitochondria-located complementary 1 Q subcomponent-binding protein, involved in mitochondrial homeostasis. Biallelic mutations in C1QBP cause mitochondrial cardiomyopathy and/or PEO with variable age of onset. Our patient showed only late-onset PEO-plus syndrome without overt cardiac involvement. Available data suggest that early-onset cardiomyopathy variants localize in important structural domains and PEO-plus variants in the coiled-coil region. Our patient demonstrates that C1QBP mutations should be considered in individuals with PEO with or without cardiomyopathy.

Keywords:

C1QBP gene; Multiple mtDNA deletions; Progressive external ophthalmoplegia; Whole exome sequencing.

Conflict of interest statement

Declaration of Competing Interest The authors declare no conflict of interest.

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