Leigh Syndrome with neonatal mild Complex IV deficiency caused by COX15 gene mutations

Sara Seneca, Kim Vancampenhout, Joél Smet, R. Vancoster, L. Dom, Urielle Ullmann, Willy Lissens, Sonia Van Dooren, Linda De Meirleir

Research output: Contribution to journalMeeting abstract (Journal)

Abstract

Isolated complex IV deficiency is a frequent cause of respiratory chain impairment and
mitochondrial disease. Onset, nature and severity of the clinical presentation or the genotype of these
patients are heterogeneous.
Here, we report clinical, biochemical and genetic data of a male infant with pathogenic mutations in
COX15. The patient was born as the 2nd child to healthy, not related parents and has an healthy
brother. He was hypotonic and presented with feeding difficulties, failure to thrive, psychomotor
retardation, lactic acidosis and cardiomyopathy. His MRI was suggestive for Leigh Disease. The
cardiomyopathy progressed rapidly and the patient died of heart failure at five months of age.
Oxidative phosphorylation (OXPHOS) enzyme activities were measured using spectrophotometrical
analysis. Biochemical analysis of the COX activity showed a very mild decrease in fibroblasts and a
low normal range value in muscle tissue. Other respiratory chain activities were normal. Functional
integrity of the five complexes was evaluated using blue native polyacrylamide gel electrophoresis
followed by in-gel activity staining in muscle tissue, and showed a decreased amount of fully
assembled CI, CII, CIII and CIV, and the presence of subassembly products of CV.
Sequencing analysis of the coding exons of the COX15 genes revealed that the patient is compound
heterozygous p.Ser151X/p.Pro302Leu. Although the number of reported COX15 mutant patients is
limited to four, the p.Ser151X mutation was previously seen in two unrelated families with a
predominant clinical presentation of cardiomyopathy. This mutation might represent a hot spot
location in the COX15 gene.
Original languageEnglish
Article numberP13.23
Pages (from-to)346-347
JournalEur J Hum Genet
Volume20
Issue numbers1
Publication statusPublished - 23 Jun 2012
EventEuropean Human Genetics Conference 2012 - Nürnberg, Germany
Duration: 23 Jun 201226 Jun 2012

Keywords

  • Leigh Syndrome
  • OXPHOS deficiency
  • COX15 gene

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