A novel homozygous pathogenic missense variant in COX6B1: Further delineation of the phenotype.

Autor: Jennions E; Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden., Olsson-Engman M; Department of Pediatrics, Blekinge Hospital, Karlskrona, Sweden., Visuttijai K; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden., Wiksell Å; Department of Pediatric Radiology, Queen Silvias Children's Hospital, Gothenburg, Sweden., Fluriach Dominguez N; Department of Pediatric Ophthalmology, Queen Silvias Children's Hospital, Gothenburg, Sweden., Kollberg G; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden., Oldfors A; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden., Hedberg-Oldfors C; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2024 Oct; Vol. 194 (10), pp. e63783. Date of Electronic Publication: 2024 Jun 06.
DOI: 10.1002/ajmg.a.63783
Abstrakt: Cytochrome c oxidase (COX) deficiency is a phenotypically diverse group of diseases caused by variants in over 30 genes. Biallelic pathogenic variants in COX6B1 have been described in four patients to date with varying disease manifestations. We describe the clinical features and follow-up of a patient with a novel homozygous pathogenic variant in COX6B1 who presented acutely with severe encephalomyopathy associated with an infection. New findings include ophthalmological evaluation and follow-up of neuroradiological investigations. The novel p.Trp31Arg variant was predicted to be pathogenic in silico, and further functional analyses with biochemical analysis of mitochondrial function showed isolated COX deficiency. Muscle biopsy showed a specific lack of COX6B1 protein together with complex IV deficiency on western blot, enzyme histochemistry, and immuno-histochemistry.
(© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
Databáze: MEDLINE