ArticleNature genetics2022
Loss of FOCAD, operating via the SKI messenger RNA surveillance pathway, causes a pediatric syndrome with liver cirrhosis.
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Genetic testing in liver diseases: Clinical applications.JHEP reports : innovation in hepatology · 2026Review
- Marine Bioactives in Liver Aging: Mechanistic Insights and Translational Potential.Marine drugs · 2026Review
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- The Diagnostic Potential and Regulatory Mechanisms of miR-3180-3p in Metabolic Dysfunction-Associated Fatty Liver Disease with Respect to Inflammation and Oxidative Stress.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- FOCAD Gene Defect Resulting in Rapidly Progressing Neonatal Liver Cirrhosis Requiring Transplant.Cureus · 2025Article
- Exome Sequencing in Adults with Unexplained Liver Disease: Diagnostic Yield and Clinical Impact.Diagnostics (Basel, Switzerland) · 2025Article
- Genomics of rare diseases in the Greater Middle East.Nature genetics · 2025Review
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- Article
- Identification of anoikis-related genes and immune infiltration characteristics in Sjögren's syndrome based on machine learning.Frontiers in medicine · 2025Article
- A Rare Case of Neonatal Cholestasis Linked to FOCAD Gene Variants: Exploring the Variable Phenotypic Presentation and Its Implications.Case reports in genetics · 2025Article
- A novel homozygous splice-site variant in theFrontiers in medicine · 2025Article
- Pediatric Perspectives on Liver Cirrhosis: Unravelling Clinical Patterns and Therapeutic Challenges.Journal of clinical medicine · 2024Review
- Review
- Genetics of liver disease in adults.Hepatology communications · 2024Review
- The role and therapeutic targeting of the CCL2/CCR2 signaling axis in inflammatory and fibrotic diseases.Frontiers in immunology · 2024Review
- Germline pathogenic variants in HNRNPU are associated with alterations in blood methylome.European journal of human genetics : EJHG · 2023Article
- Discovery of FOCAD: An Important Gene in Liver Cirrhosis.Global medical genetics · 2022Article
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47 authors at 18 institutions in 8 countries.
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Abstract
Cirrhosis is usually a late-onset and life-threatening disease characterized by fibrotic scarring and inflammation that disrupts liver architecture and function. While it is typically the result of alcoholism or hepatitis viral infection in adults, its etiology in infants is much less understood. In this study, we report 14 children from ten unrelated families presenting with a syndromic form of pediatric liver cirrhosis. By genome/exome sequencing, we found recessive variants in FOCAD segregating with the disease. Zebrafish lacking focad phenocopied the human disease, revealing a signature of altered messenger RNA (mRNA) degradation processes in the liver. Using patient's primary cells and CRISPR-Cas9-mediated inactivation in human hepatic cell lines, we found that FOCAD deficiency compromises the SKI mRNA surveillance pathway by reducing the levels of the RNA helicase SKIC2 and its cofactor SKIC3. FOCAD knockout hepatocytes exhibited lowered albumin expression and signs of persistent injury accompanied by CCL2 overproduction. Our results reveal the importance of FOCAD in maintaining liver homeostasis and disclose a possible therapeutic intervention point via inhibition of the CCL2/CCR2 signaling axis.
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