MRPL38

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: ClinGen

The relationship between *MRPL38* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of January 27, 2025. The *MRPL38* gene encodes the mitochondrial ribosomal protein L38. The first and only report of the *MRPL38* gene in relation to autosomal recessive primary mitochondrial disease was in 2022 (PMID: 35379322) in a girl with Leigh syndrome spectrum disorder. 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 two variants identified (one missense, one deletion) in one case from one publication (PMID: 35379322). This girl had Leigh syndrome spectrum disorder based on basal ganglia changes on brain imaging and neurodevelopmental delay, and also had intellectual disability, seizures, encephalopathy, and complex I and IV defects. 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). Additional functional evidence is provided in a pre-print (DOI:10.1101/2021.03.09.21253187) however this work has not yet been published. 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).