ArticleHuman genetics2023
Deficiency of the mitochondrial ribosomal subunit, MRPL50, causes autosomal recessive syndromic premature ovarian insufficiency.
Article in Human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Mrpl50 integrates glucolipotoxicity with hypoxia-inducible factor 1 alpha signaling to drive diabetic kidney disease.The Journal of biological chemistry · 2026Article
- The role of NLRP3 inflammasome in the development of postoperative ileus and its molecular mechanism in male mice.Physiological reports · 2026Article
- Comprehensive Insights into Perrault Syndrome: Genetic Diversity and Clinical Implications.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Mechanisms of mitochondrial dysfunction in premature ovarian insufficiency.Journal of ovarian research · 2026Review
- Antenatal Presentation of MRPS22-Related Mitochondrial Disease Confirmed With Rapid Proteomics.JIMD reports · 2026Article
- A biallelic MRPL42 variant causes a combined oxidative phosphorylation deficiency syndrome revealed by multi-omics.NPJ genomic medicine · 2026Article
- Sleep rescues age-associated loss of glial engulfment.PLoS genetics · 2026Article
- Untargeted proteomics enables ultra-rapid variant prioritisation in mitochondrial and other rare diseases.Genome medicine · 2025Article
- Endocrine Dysfunction in Primary Mitochondrial Diseases.Endocrine reviews · 2025Review
- Bi-allelic variants in MRPL49 cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency.American journal of human genetics · 2025Article
- Review: Utility of mass spectrometry in rare disease research and diagnosis.NPJ genomic medicine · 2025Review
- Bi-allelic variants in DAP3 result in reduced assembly of the mitoribosomal small subunit with altered apoptosis and a Perrault-syndrome-spectrum phenotype.American journal of human genetics · 2025Article
- Endocrine system disturbances in children with inherited metabolic diseases: a narrative review.Frontiers in endocrinology · 2025Review
- A micro-costing study of mass-spectrometry based quantitative proteomics testing applied to the diagnostic pipeline of mitochondrial and other rare disorders.Orphanet journal of rare diseases · 2024Article
- Integrative bioinformatics analysis for identifying the mitochondrial-related gene signature associated with immune infiltration in premature ovarian insufficiency.BMC medicine · 2024Article
- Premature ovarian insufficiency.Nature reviews. Disease primers · 2024Review
- Biallelic variants inmedRxiv : the preprint server for health sciences · 2024Article
- Supernumerary proteins of the human mitochondrial ribosomal small subunit are integral for assembly and translation.iScience · 2024Article
- Primary ovarian insufficiency: update on clinical and genetic findings.Frontiers in endocrinology · 2024Review
- Molecular pathways in mitochondrial disorders due to a defective mitochondrial protein synthesis.Frontiers in cell and developmental biology · 2024Review
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Authors and funding
26 authors at 6 institutions in 3 countries.
Funding
Abstract
Premature ovarian insufficiency (POI) is a common cause of infertility in women, characterised by amenorrhea and elevated FSH under the age of 40 years. In some cases, POI is syndromic in association with other features such as sensorineural hearing loss in Perrault syndrome. POI is a heterogeneous disease with over 80 causative genes known so far; however, these explain only a minority of cases. Using whole-exome sequencing (WES), we identified a MRPL50 homozygous missense variant (c.335T > A; p.Val112Asp) shared by twin sisters presenting with POI, bilateral high-frequency sensorineural hearing loss, kidney and heart dysfunction. MRPL50 encodes a component of the large subunit of the mitochondrial ribosome. Using quantitative proteomics and western blot analysis on patient fibroblasts, we demonstrated a loss of MRPL50 protein and an associated destabilisation of the large subunit of the mitochondrial ribosome whilst the small subunit was preserved. The mitochondrial ribosome is responsible for the translation of subunits of the mitochondrial oxidative phosphorylation machinery, and we found patient fibroblasts have a mild but significant decrease in the abundance of mitochondrial complex I. These data support a biochemical phenotype associated with MRPL50 variants. We validated the association of MRPL50 with the clinical phenotype by knockdown/knockout of mRpL50 in Drosophila, which resulted abnormal ovarian development. In conclusion, we have shown that a MRPL50 missense variant destabilises the mitochondrial ribosome, leading to oxidative phosphorylation deficiency and syndromic POI, highlighting the importance of mitochondrial support in ovarian development and function.
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