Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia,...

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Published inAnnals of clinical and translational neurology Vol. 6; no. 1; pp. 154 - 160
Main Authors Otero, Maria G., Tiongson, Emmanuelle, Diaz, Frank, Haude, Katrina, Panzer, Karin, Collier, Ashley, Kim, Jaemin, Adams, David, Tifft, Cynthia J., Cui, Hong, Millian Zamora, Francisca, Au, Margaret G., Graham, John M., Buckley, David J., Lewis, Richard, Toro, Camilo, Bai, Renkui, Turner, Lesley, Mathews, Katherine D., Gahl, William, Pierson, Tyler Mark
Format Journal Article
LanguageEnglish
Published United States John Wiley and Sons Inc 01.01.2019
Subjects
Adolescent
Adult
Ataxia - genetics
Brief Communication
Brief Communications
Child
Dysarthria - genetics
Electron Transport Complex IV - genetics
Female
Hereditary Sensory and Autonomic Neuropathies - genetics
Humans
Male
Pedigree
Phenotype
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ISSN2328-9503
2328-9503
DOI10.1002/acn3.661

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Summary:COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron‐one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron‐two. cDNA and protein analysis indicated that no full‐length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency.
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Contributed equally to this work.
During this study D.A., C.J.T. & C.T. were supported by the National Institutes of Health Undiagnosed Diseases Network; W.A.G. was supported by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health. TMP was funded by Cedars‐Sinai Institutional funding program and the Cedars‐Sinai Diana and Steve Marienhoff Fashion Industries Guild Endowed Fellowship in Pediatric Neuromuscular Diseases.
ISSN:2328-9503
2328-9503
DOI:10.1002/acn3.661