MRPL24

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: ClinGen

The relationship between *MRPL24* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of January 27, 2025. The *MRPL24* gene encodes the mitochondrial ribosomal protein L24. The first and only report of the *MRPL24* gene in relation to autosomal recessive primary mitochondrial disease was in 2020 (PMID: 32344152), in a girl with cerebellar atrophy, choreoathetosis, intellectual disability and combined complex I and IV deficiency. This is one disease entity according to the ClinGen Lumping and Splitting Framework, and is considered a primary mitochondrial disease. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included one homozygous missense variant identified in one case from one publication (PMID: 32344152). This girl had normal development until age 8 months when she experienced developmental regression (lost ability to sit and vocalize). By age 3 years, she had spasticity, dystonic posturing of distal upper and lower limbs, and dyskinetic facial grimacing. By age 8 years, she was sitting with support. She also had intellectual disability with lack of interaction with the environment and behavioral disturbance. Her course was stable at 14 years. Brain imaging at age three years showed bilateral alterations at the level of the putamen and cerebellar atrophy. She had elevated plasma lactate and decreased mitochondrial respiratory chain activities (combined defect of complexes I and IV) in skeletal muscle and cultured skin fibroblasts. The mechanism of disease is loss of function. This gene-disease relationship is also supported by a biochemical function shared with other genes associated with primary mitochondrial disease (PMID: 33340416) and a zebrafish model (PMID: 32344152). In summary, there is limited evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel January 27, 2025 (SOP Version 11).