PET100 and Mitochondrial Disease

PET100 (HGNC:40038) has been implicated in mitochondrial disease (MONDO:0044970) based on a homozygous truncating variant identified in a patient from a consanguineous British Asian family (PMID:25293719). The reported variant, c.142C>T (p.Gln48Ter), leads to a complete loss of cytochrome c oxidase activity and failure to assemble the holocomplex, which is consistent with the patient’s presentation of fatal infantile lactic acidosis. Although the genetic evidence is currently limited to a single proband, the variant’s predicted loss‐of‑function effect is strongly supported by functional assays that demonstrated abolished enzyme activity. The study additionally reinforces the mechanism of pathogenicity by showing that the truncating PET100 allele disrupts mitochondrial complex IV assembly. No additional affected relatives were documented beyond the index case, limiting the segregation evidence. Further independent studies are required to extend the phenotypic spectrum and validate the association in a broader patient population. Despite the presently limited data, the concurrence of genetic and functional evidence highlights the diagnostic utility of screening PET100 variants in patients with isolated mitochondrial complex IV deficiency.

Key Take‑home: The homozygous c.142C>T (p.Gln48Ter) variant in PET100 is a critical diagnostic marker for mitochondrial disease in patients with neonatal-onset lactic acidosis and cytochrome c oxidase deficiency.

References

• European journal of human genetics : EJHG • 2015 • A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency PMID:25293719

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