ArticleHuman genetics2016
Spectrum of mutations and genotype-phenotype analysis in Noonan syndrome patients with RIT1 mutations.
Article in Human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 99 citations in OpenAlex.
- Update on the Clinical and Molecular Characterization of Noonan Syndrome and Other RASopathies: A Retrospective Study and Systematic Review.International journal of molecular sciences · 2025Pooled it
- Williams-Beuren syndrome in diverse populations.American journal of medical genetics. Part A · 2018Pooled it
- Clinical consensus guidelines for the management of Noonan syndrome in Japan.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2026Article
- Clinical and Molecular Portraits of Pediatric RASopathies: A Study of 118 Genotype-Confirmed Cases.Clinical genetics · 2026Article
- Article
- Neonatal Noonan syndrome with acute kidney injury and systemic capillary leak syndrome caused by aFrontiers in pediatrics · 2026Article
- Phenotypic Analysis of Embryos in a Noonan Syndrome Model Mouse With the Rit1 A57G Mutation.Molecular genetics & genomic medicine · 2025Article
- Ubiquitin-independent pathway regulates the RIT1-MAPK pathway in chordoma progression.Cell death & disease · 2025Article
- Modulating PAK1: Accessory Proteins as Promising Therapeutic Targets.Biomolecules · 2025Review
- Clinical features and molecular genetics of patients with RASopathies: expanding the phenotype with rare genes and novel variants.European journal of pediatrics · 2024Article
- Refractory Chylothorax and Ventricular Hypertrophy Treated with Trametinib in a Patient with Noonan Syndrome: 18-Month Follow-Up.Children (Basel, Switzerland) · 2024Article
- Computer-based facial recognition as an assisting diagnostic tool to identify children with Noonan syndrome.BMC pediatrics · 2024Article
- Genetic backgrounds and genotype-phenotype relationships in anthropometric parameters of 116 Japanese individuals with Noonan syndrome.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2024Article
- RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome-associated cardiac hypertrophy.Science advances · 2023Article
- Dilated coronary arteries in a 2-month-old with RIT1-associated Noonan syndrome: a case report.BMC pediatrics · 2023Article
- A case of non-immune hydrops fetalis with maternal mirror syndrome diagnosed by trio-based exome sequencing: An autopsy case report and literature review.Molecular genetics and metabolism reports · 2022Article
- Lymphatic anomalies during lifetime in patients with Noonan syndrome: Retrospective cohort study.American journal of medical genetics. Part A · 2022Article
- Article
- Molecular and clinical profile of patients referred as Noonan or Noonan-like syndrome in Greece: a cohort of 86 patients.European journal of pediatrics · 2022Article
- Pathological MAPK activation-mediated lymphatic basement membrane disruption causes lymphangiectasia that is treatable with ravoxertinib.JCI insight · 2022Article
Corrections and comments
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Authors and funding
26 authors at 19 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RASopathies are autosomal dominant disorders caused by mutations in more than 10 known genes that regulate the RAS/MAPK pathway. Noonan syndrome (NS) is a RASopathy characterized by a distinctive facial appearance, musculoskeletal abnormalities, and congenital heart defects. We have recently identified mutations in RIT1 in patients with NS. To delineate the clinical manifestations in RIT1 mutation-positive patients, we further performed a RIT1 analysis in RASopathy patients and identified 7 RIT1 mutations, including two novel mutations, p.A77S and p.A77T, in 14 of 186 patients. Perinatal abnormalities, including nuchal translucency, fetal hydrops, pleural effusion, or chylothorax and congenital heart defects, are observed in all RIT1 mutation-positive patients. Luciferase assays in NIH 3T3 cells demonstrated that the newly identified RIT1 mutants, including p.A77S and p.A77T, and the previously identified p.F82V, p.T83P, p.Y89H, and p.M90I, enhanced Elk1 transactivation. Genotype-phenotype correlation analyses of previously reported NS patients harboring RIT1, PTPN11, SOS1, RAF1, and KRAS revealed that hypertrophic cardiomyopathy (56 %) was more frequent in patients harboring a RIT1 mutation than in patients harboring PTPN11 (9 %) and SOS1 mutations (10 %). The rates of hypertrophic cardiomyopathy were similar between patients harboring RIT1 mutations and patients harboring RAF1 mutations (75 %). Short stature (52 %) was less prevalent in patients harboring RIT1 mutations than in patients harboring PTPN11 (71 %) and RAF1 (83 %) mutations. These results delineate the clinical manifestations of RIT1 mutation-positive NS patients: high frequencies of hypertrophic cardiomyopathy, atrial septal defects, and pulmonary stenosis; and lower frequencies of ptosis and short stature.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.