ArticleHuman genetics2019
Delineation of LZTR1 mutation-positive patients with Noonan syndrome and identification of LZTR1 binding to RAF1-PPP1CB complexes.
Article in Human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 3 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Pooled it
- 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
- Abnormalities of pubertal development and gonadal function in Noonan syndrome.Frontiers in endocrinology · 2023Pooled it
- Clinical and Molecular Portraits of Pediatric RASopathies: A Study of 118 Genotype-Confirmed Cases.Clinical genetics · 2026Article
- Article
- 22q11.2 duplication syndrome and LZTR1-related Noonan syndrome type 10 overlapping phenotypes in a dual diagnosis - fetal hydrops: a case report.BMC pregnancy and childbirth · 2026Article
- Pathogenesis of Noonan Syndrome is Modulated by NOC2L, a Novel Interactor of LZTR1 Leading to Impaired P53 Signalling.The Journal of clinical endocrinology and metabolism · 2026Article
- Genotype-Phenotype Analysis and New Clinical Findings in a Series of 24 Patients Presenting with Noonan Syndrome and Related Disorders.Molecular syndromology · 2026Article
- Article
- Structural basis for LZTR1 recognition of RAS GTPases for degradation.Science (New York, N.Y.) · 2025Article
- Abernethy malformation (Type II) presenting in a 6-day-old boy with Noonan syndrome: a case report.BMC pediatrics · 2025Article
- Complete commissural agenesis in a child with Noonan-like syndrome with loose anagen hair 2.Neurogenetics · 2025Article
- Missense and truncated variants in ERF in individuals with a Noonan-like phenotype without craniosynostosis.Scientific reports · 2025Article
- Nerve Enlargement in Patients with INF2 Variants Causing Peripheral Neuropathy and Focal Segmental Glomerulosclerosis.Biomedicines · 2025Article
- Updated ACMG/AMP specifications for variant interpretation and gene curations from the ClinGen RASopathy expert panels.Genetics in medicine open · 2025Article
- Biventricular outflow tract obstruction due to hypertrophy related to compound heterozygous variants in LZTR1.ESC heart failure · 2024Article
- Dysregulation of RAS proteostasis by autosomal-dominant LZTR1 mutation induces Noonan syndrome-like phenotypes in mice.JCI insight · 2024Article
- Phenotypic Expansion of Autosomal DominantGenes · 2024Review
- Macrocephaly and Finger Changes: A Narrative Review.International journal of molecular sciences · 2024Review
- Preclinical evaluation of CRISPR-based therapies for Noonan syndrome caused by deep-intronicMolecular therapy. Nucleic acids · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RASopathies are a group of developmental disorders caused by mutations in genes that regulate the RAS/MAPK pathway and include Noonan syndrome (NS), Costello syndrome, cardiofaciocutaneous syndrome and other related disorders. Whole exome sequencing studies recently identified LZTR1, PPP1CB and MRAS as new causative genes in RASopathies. However, information on the phenotypes of LZTR1 mutation-positive patients and functional properties of the mutations are limited. To identify variants of LZTR1, PPP1CB, and MRAS, we performed a targeted next-generation sequencing and reexamined previously analyzed exome data in 166 patients with suspected RASopathies. We identified eight LZTR1 variants, including a de novo variant, in seven probands who were suspicious for NS and one known de novo PPP1CB variant in a patient with NS. One of the seven probands had two compound heterozygous LZTR1 variants, suggesting autosomal recessive inheritance. All probands with LZTR1 variants had cardiac defects, including hypertrophic cardiomyopathy and atrial septal defect. Five of the seven probands had short stature or intellectual disabilities. Immunoprecipitation of endogenous LZTR1 followed by western blotting showed that LZTR1 bound to the RAF1-PPP1CB complex. Cells transfected with a small interfering RNA against LZTR1 exhibited decreased levels of RAF1 phosphorylated at Ser259. These are the first results to demonstrate LZTR1 in association with the RAF1-PPP1CB complex as a component of the RAS/MAPK pathway.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.