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Published on: August 24, 2013

Expanding the MRPS34 Genotype-Phenotype Correlation: Two Novel Cases and a Cohort Review

Alberte Aspaas Lundquist1,2,3,4, Sumit Parikh5, Thomas van Overeem Hansen1,4

  • 1Department of Clinical Genetics, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.

JIMD Reports
|June 10, 2026
PubMed

Insights

Pathogenic variants in MRPS34 cause Combined Oxidative Phosphorylation Deficiency 32 (COXPD32), a rare mitochondrial disorder. This study details two new cases, expanding the known clinical and genetic spectrum of COXPD32.

Area of Science:

  • Genetics
  • Mitochondrial Biology
  • Neurology

Background:

  • MRPS34 encodes a mitoribosomal protein crucial for mitochondrial translation.
  • Biallelic pathogenic variants in MRPS34 lead to Combined Oxidative Phosphorylation Deficiency 32 (COXPD32), a Leigh Syndrome Spectrum disorder.
  • COXPD32 exhibits a wide clinical spectrum, from infantile fatality to adult survival.

Purpose of the Study:

  • To describe two novel individuals with MRPS34-related disease.
  • To expand the clinical, genetic, and phenotypic spectrum of COXPD32.
  • To explore genotype-phenotype correlations in MRPS34-related disease.

Main Methods:

  • Clinical, radiological, biochemical, and molecular evaluations of two patients with Leigh Syndrome.
  • Exome and genome sequencing to identify MRPS34 variants.
  • Systematic review of 11 previously reported cases.

Main Results:

  • Two individuals with Leigh Syndrome were identified with presumed biallelic MRPS34 variants.
  • Individual 1, deceased in infancy, had a novel splice-site and a nonsense variant.
  • Individual 2, surviving into mid-childhood, was homozygous for a hypomorphic variant (c.322-10G>A).
  • Key features across 11 individuals included developmental delay, lactic acidosis, brainstem lesions, and metabolic acidosis.
  • Homozygosity for c.322-10G>A correlated with longer survival.

Conclusions:

  • MRPS34-related disease presents with multisystemic features and genotype-dependent severity.
  • Accurate genetic diagnosis is crucial for prognosis and guiding therapeutic strategies.
  • This study expands the understanding of COXPD32's clinical and genetic landscape.
Keywords:
MRPS34combined oxidative phosphorylation deficiency 32genotype–phenotype correlationhypomorphic splice variantleigh syndrome spectrummitochondrial disease

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