Open AccessNovel pathogenic COX 20 variants causing dysarthria, ataxia, and sensory neuropathy
Author(s) -
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
Publication year - 2019
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.661
Subject(s) - missense mutation , hypotonia , genetics , exome sequencing , medicine , ataxia , dystonia , intron , dysarthria , splice site mutation , phenotype , splice , exon , gene , biology , alternative splicing , audiology , psychiatry
Abstract COX 20/ FAM 36A encodes a mitochondrial complex IV assembly factor important for COX 2 activation. Only one homozygous COX 20 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 COX 20 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 COX 20 deficiency.