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Update on the Clinical and Molecular Characterization of Noonan Syndrome and Other RASopathies: A Retrospective Study and Systematic Review.

作者信息

Reynolds Giuseppe, Gazzin Andrea, Carli Diana, Massuras Stefania, Cardaropoli Simona, Luca Maria, Defilippi Beatrice, Tartaglia Marco, Ferrero Giovanni Battista, Mussa Alessandro

机构信息

Department of Public Health and Pediatrics, Postgraduate School of Pediatrics, University of Torino, 10126 Turin, Italy.

Department of Public Health and Pediatric Sciences, University of Torino, 10126 Turin, Italy.

出版信息

Int J Mol Sci. 2025 Apr 9;26(8):3515. doi: 10.3390/ijms26083515.


DOI:10.3390/ijms26083515
PMID:40332000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12027154/
Abstract

RASopathies are a diverse group of genetic conditions caused by hyperactivation of the RAS-MAPK signaling pathway, mainly inherited in an autosomal dominant manner. They present with variable features such as short stature, congenital heart defects, facial dysmorphisms, and neurodevelopmental delays. This study retrospectively analyzed 143 cases from 2003 to 2022, aiming to improve genotype-phenotype correlation knowledge for personalized care. Patients with genetically confirmed Noonan syndrome (NS) and related disorders were included, with molecular analysis performed via Sanger or parallel sequencing. Data from 906 previously reported cases were also reviewed. Among the 143 patients, most had NS ( = 116). mutations were most frequent (61%), followed by (10.3%) and (8.6%). Cardiac anomalies were observed in 71%, with pulmonary stenosis (PS) prevalent in NS (48.3%) and hypertrophic cardiomyopathy (HCM) in NSML (40%). variants were linked to PS and atrial septal defects, to multiple cardiopathies, and to HCM. Additional features included facial dysmorphisms (74.1%), short stature (62.0%), skeletal anomalies (43.1%), cryptorchidism (59.7%), and brain abnormalities (17.2%). JMML and other malignancies were seen in eight patients. This study emphasizes the importance of genotype-guided care, improved diagnosis of mild cases, and the underrecognized prevalence of neurological anomalies.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dc/12027154/ddf757659aec/ijms-26-03515-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dc/12027154/53df98c702bc/ijms-26-03515-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dc/12027154/58ccacec4641/ijms-26-03515-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dc/12027154/ddf757659aec/ijms-26-03515-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dc/12027154/53df98c702bc/ijms-26-03515-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dc/12027154/58ccacec4641/ijms-26-03515-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3dc/12027154/ddf757659aec/ijms-26-03515-g003.jpg

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[1]
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Front Oncol. 2024-9-6

[2]
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Clin Cancer Res. 2024-11-1

[3]
Loss-of-function variants in ERF are associated with a Noonan syndrome-like phenotype with or without craniosynostosis.

Eur J Hum Genet. 2024-8

[4]
Defining the variant-phenotype correlation in patients affected by Noonan syndrome with the RAF1:c.770C>T p.(Ser257Leu) variant.

Eur J Hum Genet. 2024-8

[5]
The molecular genetics of RASopathies: An update on novel disease genes and new disorders.

Am J Med Genet C Semin Med Genet. 2022-12

[6]
A severe clinicopathologic phenotype of RAF1 Ser257Leu neomutation in a preterm infant without cardiac anomaly.

Am J Med Genet A. 2023-2

[7]
Cancer-causing MAP2K1 mutation in a mosaic patient with cardio-facio-cutaneous syndrome and immunodeficiency.

Hum Mutat. 2022-12

[8]
Cutaneous manifestations in Costello syndrome: HRAS p.Gly12Ser affects RIN1-mediated integrin trafficking in immortalized epidermal keratinocytes.

Hum Mol Genet. 2023-1-6

[9]
Molecular and clinical profile of patients referred as Noonan or Noonan-like syndrome in Greece: a cohort of 86 patients.

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[10]
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