ArticleAmerican journal of human genetics2019
RINT1 Bi-allelic Variations Cause Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 55 citations in OpenAlex.
- Functional analysis of novel and recurrent RINT1 variants in patients with infantile liver dysfunction.Journal of human genetics · 2026Article
- The Evolving Trend of Liver Transplantation in Metabolic Diseases: From Origins to Current Perspectives.Journal of inherited metabolic disease · 2025Review
- Recurrent acute liver failure and neutropenia caused by a novel homozygous RINT1 variant: a brief report of phenotypic expansion and population-specific findings.Human genomics · 2025Article
- Paediatric acute liver failure: A prospective, nationwide, population-based surveillance study in Germany.Journal of pediatric gastroenterology and nutrition · 2025Article
- Cytokine-Induced Cytotoxicity and Extracellular Matrix Abnormalities in Hepatocytes Derived From RAD50-Interacting Protein 1-Deficient Induced Pluripotent Stem Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Germline variants detected by multigene panel testing in patients with suspected hereditary breast cancer.Surgery today · 2025Article
- Skeletal dysplasia-causing mutations in TRPV4 alter the chondrocyte transcriptomic response to mechanical loading.American journal of physiology. Cell physiology · 2025Article
- Recurrent fever-associated acute liver failure and cranial dysmorphism in children caused by RINT1 gene mutations: a rare case report.Frontiers in pediatrics · 2025Article
- Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency.Journal of inherited metabolic disease · 2025Review
- Fever Triggered Recurrent Acute Liver Failure due to RINT1 Deficiency.Indian journal of pediatrics · 2024Article
- The diagnostic yield of exome sequencing in liver diseases from a curated gene panel.Scientific reports · 2023Article
- Acute infantile liver failure syndrome type 2 in a 2.5-year-old boy: A case report.Clinical case reports · 2023Article
- RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia.The Journal of clinical investigation · 2023Article
- Challenges in pediatric inherited/metabolic liver disease: Focus on the disease spectrum, diagnosis and management of relatively common disorders.World journal of gastroenterology · 2023Review
- A novel variant in NBAS identified from an infant with fever-triggered recurrent acute liver failure disrupts the function of the gene.Human genome variation · 2023Article
- Genome-scale CRISPR screening in a single mouse liver.Cell genomics · 2022Article
- Pathogenic mutations in the chromokinesin KIF22 disrupt anaphase chromosome segregation.eLife · 2022Article
- A mysterious cause of recurrent acute liver dysfunction for over a decade.Gastroenterology report · 2022Article
- Impact of integrated translational research on clinical exome sequencing.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Novel compound heterozygous variants in theBMJ case reports · 2021Article
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Authors and funding
29 authors at 12 institutions in 4 countries.
Funding
Abstract
Pediatric acute liver failure (ALF) is life threatening with genetic, immunologic, and environmental etiologies. Approximately half of all cases remain unexplained. Recurrent ALF (RALF) in infants describes repeated episodes of severe liver injury with recovery of hepatic function between crises. We describe bi-allelic RINT1 alterations as the cause of a multisystem disorder including RALF and skeletal abnormalities. Three unrelated individuals with RALF onset ≤3 years of age have splice alterations at the same position (c.1333+1G>A or G>T) in trans with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del) in RINT1. ALF episodes are concomitant with fever/infection and not all individuals have complete normalization of liver function testing between episodes. Liver biopsies revealed nonspecific liver damage including fibrosis, steatosis, or mild increases in Kupffer cells. Skeletal imaging revealed abnormalities affecting the vertebrae and pelvis. Dermal fibroblasts showed splice-variant mediated skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay. Fibroblasts also revealed decreased RINT1 protein, abnormal Golgi morphology, and impaired autophagic flux compared to control. RINT1 interacts with NBAS, recently implicated in RALF, and UVRAG, to facilitate Golgi-to-ER retrograde vesicle transport. During nutrient depletion or infection, Golgi-to-ER transport is suppressed and autophagy is promoted through UVRAG regulation by mTOR. Aberrant autophagy has been associated with the development of similar skeletal abnormalities and also with liver disease, suggesting that disruption of these RINT1 functions may explain the liver and skeletal findings. Clarifying the pathomechanism underlying this gene-disease relationship may inform therapeutic opportunities.
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