MRPS23 – Mitochondrial Disease

This summary outlines the association between MRPS23 and mitochondrial disease. MRPS23, a nuclear gene encoding a mitochondrial ribosomal protein, has been implicated in a mitochondrial disorder that presents with a constellation of metabolic and neurological abnormalities. The observed phenotype encompasses hypoglycemia, lactic acidosis, reduced consciousness, decreased liver function, and hearing impairment. The association is supported by data from multi‐patient studies and functional assays, underscoring the clinical relevance of MRPS23 in the mitochondrial disease spectrum (PMID:38086984)

Genetic evidence has demonstrated that five unrelated probands were identified with a homozygous c.119C>T (p.Pro40Leu) variant in MRPS23 (PMID:38086984). In addition, segregation analysis in a Hmong hilltribe revealed eight family members homozygous for the variant, of whom seven exhibited clinical manifestations consistent with mitochondrial dysfunction (PMID:38086984). This robust observation contributes to a strong genetic evidence base.

The detailed genetic study reported a consistent variant spectrum in MRPS23 with the specific variant c.119C>T (p.Pro40Leu) being recurrent across unrelated patients. The variant, when present in a homozygous state, correlates with the mitochondrial phenotype, emphasizing the role of recessive inheritance in this disorder. Moreover, the phenotypic presentation among the probands reflects a broad clinical spectrum that aligns with mitochondrial dysfunction, lending further support to the gene–disease link.

Functional assessments have been pivotal in establishing the pathogenicity of the MRPS23 variant. In vitro assays in cultured skin fibroblasts revealed a significant deficiency in respiratory chain complexes I and IV, consistent with the biochemical signature of mitochondrial disorders (PMID:38086984). These findings indicate that the c.119C>T (p.Pro40Leu) variant likely disrupts mitochondrial protein synthesis, thus compromising energy production.

Integrating both the genetic and functional evidence, it is clear that MRPS23 plays a critical role in the pathogenesis of a mitochondrial disorder inherited in an autosomal recessive manner. Although additional studies have identified MRPS23 as a novel candidate in broader genomic analyses of mitochondrial respiratory chain deficiencies (PMID:26741492), the direct evidence from the recent case series reinforces the clinical utility of MRPS23 testing in patients meeting the phenotypic criteria.

Key take‐home message: The homozygous c.119C>T (p.Pro40Leu) variant in MRPS23 provides strong evidence for causation of a mitochondrial disorder, supporting its use in diagnostic decision‑making and offering a clear pathway for tailored patient management.

References

• Scientific Reports • 2023 • Genetic, metabolic and clinical delineation of an MRPS23-associated mitochondrial disorder PMID:38086984
• PLoS Genetics • 2016 • A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies PMID:26741492

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