Biallelic variants in COX4I1 associated with a novel phenotype resembling Leigh syndrome with developmental regression, intellectual disability, and seizures

Nishitha R. Pillai, Noura S. AlDhaheri, Rajarshi Ghosh, Jaehyung Lim, Haley Streff, Anuranjita Nayak, Brett H. Graham, Neil A. Hanchard, Sarah H. Elsea, Fernando Scaglia

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2138-2143
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume179
Issue number10
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank the patients, their family and all physicians involved in their care.

Keywords

  • COX4I1
  • Leigh syndrome
  • cytochrome c oxidase
  • mitochondrial disease

PubMed: MeSH publication types

  • Case Reports
  • Journal Article

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