ArticleAmerican journal of medical genetics. Part A2016
A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair.
Article in American journal of medical genetics. Part A, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.
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Who cites it
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 150 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
- Genotype-Phenotype Analysis and New Clinical Findings in a Series of 24 Patients Presenting with Noonan Syndrome and Related Disorders.Molecular syndromology · 2026Article
- Molecular characterization of individuals with RASopathies: Spectrum of genetic variants in a large Indian cohort.Journal of genetics · 2026Article
- Complete commissural agenesis in a child with Noonan-like syndrome with loose anagen hair 2.Neurogenetics · 2025Article
- Mechanisms of brain overgrowth in autism spectrum disorder with macrocephaly.Frontiers in neuroscience · 2025Review
- Clinical features and molecular genetics of patients with RASopathies: expanding the phenotype with rare genes and novel variants.European journal of pediatrics · 2024Article
- Loss-of-function variants in ERF are associated with a Noonan syndrome-like phenotype with or without craniosynostosis.European journal of human genetics : EJHG · 2024Article
- RASopathies - what they reveal about RAS/MAPK signaling in skeletal muscle development.Disease models & mechanisms · 2024Review
- RAS and SHOC2 Roles in RAF Activation and Therapeutic Considerations.Annual review of cancer biology · 2024Article
- Prenatal and infantile diagnosis of craniosynostosis in individuals with RASopathies.American journal of medical genetics. Part A · 2024Article
- Structural insights into the role of SHOC2-MRAS-PP1C complex in RAF activation.The FEBS journal · 2023Review
- Genotypic Findings in Noonan and Non-Noonan RASopathies and Patient Eligibility for Growth Hormone Treatment.Journal of clinical medicine · 2023Article
- Familial and syndromic forms of arachnoid cyst implicate genetic factors in disease pathogenesis.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- The molecular genetics of RASopathies: An update on novel disease genes and new disorders.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
- Cancer incidence and surveillance strategies in individuals with RASopathies.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
- Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan syndrome.Nature structural & molecular biology · 2022Article
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3 more citing papers are in PubMed but not listed here.
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10 authors at 3 institutions in 1 country.
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Abstract
Noonan syndrome is a rasopathy caused by mutations in multiple genes encoding components of the RAS/MAPK pathway. Despite its variable phenotype, limited genotype-phenotype correlations exist. Noonan syndrome with loose anagen hair (NS-LAH) is characterized by its distinctive hair anomalies, developmental differences, and structural brain abnormalities and is caused by a single recurrent missense SHOC2 mutation. SHOC2 forms a complex with protein phosphatase 1 (PP1C). Protein phosphatases counterbalance kinases and control activation of signaling proteins, such as the mitogen-activated protein kinases of the RAS/MAPK pathway. Here we report four patients with de novo missense mutations in protein phosphatase one catalytic subunit beta (PPP1CB), sharing a recognizable phenotype. Three individuals had the recurrent PPP1CB c.146G>C, p.Pro49Arg mutation, the fourth had a c.166G>C, p.Ala56Pro change. All had relative or absolute macrocephaly, low-set and posteriorly angulated ears, and developmental delay. Slow growing and/or sparse hair and/or an unruly hair texture was present in all. Three individuals had feeding difficulties requiring feeding tubes. One of two males had cryptorchidism, another had pectus excavatum. Short stature was present in three. A female with the recurrent mutation had a Dandy-Walker malformation and optic nerve hypoplasia. Mild ventriculomegaly occurred in all, cerebellar tonsillar ectopia was seen in two and progressed to Chiari 1 malformation in one individual. Based on the combination of phenotypic findings and PPP1CB's effect on RAF dephosphorylation within the RAS/MAPK pathway, this novel condition can be considered a rasopathy, most similar to NS-LAH. Collectively, these mutations meet the standardized criteria for pathogenicity. © 2016 Wiley Periodicals, Inc.
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