LYRM7 - associated complex III deficiency: A clinical, molecular genetic, MR tomographic, and biochemical study.

LYRM7 is involved in the last steps of mitochondrial complex III assembly where it acts as a chaperone for the Rieske iron‑sulfur (Fe-S) protein in the mitochondrial matrix. Using exome sequencing, we identified homozygosity for a splice site destroying 4 base pair deletion in LYRM7 in a child with recurrent lactic acidotic crises and distinct early-onset leukencephalopathy. Sanger sequencing showed variant segregation in similarly affected family members. Functional analyses revealed a reduced amount of the Rieske Fe-S protein, which was restored after re-expression of LYRM7 . Our data provide further evidence for the importance of LYRM7 for mitochondrial function and emphasize the importance of whole exome sequencing in the diagnosis of rare mitochondrial diseases. [ABSTRACT FROM AUTHOR]