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Biallelic variants in COX4I1 associated with a novel phenotype resembling Leigh syndrome with developmental regression, intellectual disability, and seizures
Author(s) -
Pillai Nishitha R.,
AlDhaheri Noura S.,
Ghosh Rajarshi,
Lim Jaehyung,
Streff Haley,
Nayak Anuranjita,
Graham Brett H.,
Hanchard Neil A.,
Elsea Sarah H.,
Scaglia Fernando
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61288
Subject(s) - cytochrome c oxidase , phenotype , biology , hypotonia , genetics , gene , mitochondrion
Abstract Autosomal recessive COX4I1 deficiency has been previously reported in a single individual with a homozygous pathogenic variant in COX4I1 , who presented with short stature, poor weight gain, dysmorphic features, and features of Fanconi anemia. COX4I1 encodes subunit 4, isoform 1 of cytochrome c oxidase. Cytochrome c oxidase is a respiratory chain enzyme that plays an important role in mitochondrial electron transport and reduces molecular oxygen to water leading to the formation of ATP. Defective production of cytochrome c oxidase leads to a variable phenotypic spectrum ranging from isolated myopathy to Leigh syndrome. Here, we describe two siblings, born to consanguineous parents, who presented with encephalopathy, developmental regression, hypotonia, pathognomonic brain imaging findings resembling Leigh‐syndrome, and a novel homozygous variant on COX4I1 , expanding the known clinical phenotype associated with pathogenic variants in COX4I1 .