Publication Name	World Journal of Cardiology
Manuscript ID	106525
Country	China

Category	Cardiac & Cardiovascular Systems
Manuscript Type	Case Report
Article Title	RAF1 mutation expands the cardiac phenotypic spectrum of Noonan syndrome: A case report
Manuscript Source	Unsolicited Manuscript
All Author List	Nan Ma, Zhong-Wei Li, Jia-Jia Liu, Xing-Guang Liu, Xing Zhou, Bo-Wen Wang, Yan-Ling Li, Tian-Cheng Zhang and Ping Xie
Funding Agency and Grant Number	Funding Agency Grant Number Gansu Provincial Science and Technology Plan Project No. 24JRRA886 and No. 23JRRA1287 Gansu Provincial People’s Hospital: Excellent Doctoral Student Cultivation Program No. 22GSSYD-14
Corresponding Author	Ping Xie, Chief Physician, Full Professor, MD, Department of Cardiovascular Medicine, Gansu Provincial Hospital, No. 204 Donggang West Road, Lanzhou 730000, Gansu Province, China. pingxie66@163.com
Key Words	Noonan syndrome; RAF1 gene mutation; Hypertrophic cardiomyopathy; Atrial septal defect; Ventricular septal defect; Case report
Core Tip	This case report elucidates the unique clinical heterogeneity of the RAF1 c.770C > T (p.Ser257 Leu) mutation in Noonan syndrome. While this variant is classically associated with severe hypertrophic cardiomyopathy and pulmonary hypertension, our patient exhibited atypical congenital heart defects - including atrial septal defect and ventricular septal defect - coexisting with hypertrophic cardiomyopathy, suggesting potential dysregulation of alternative molecular pathways in cardiac morphogenesis. Notably, this case expands the phenotypic spectrum of RAF1 mutations, underscoring the necessity for comprehensive genetic counseling even in carriers of “classic” mutations, as genotype-phenotype correlations remain incompletely defined. Mechanistically, we propose that this mutation disrupts RAF1 protein-mediated mitogen-activated protein kinase signaling, thereby contributing to aberrant cardiac developmental pathways.
Citation	Ma N, Li ZW, Liu JJ, Liu XG, Zhou X, Wang BW, Li YL, Zhang TC, Xie P. RAF1 mutation expands the cardiac phenotypic spectrum of Noonan syndrome: A case report. World J Cardiol 2025; In press

Received	2025-03-07 11:22
Peer-Review Started	2025-03-07 11:22
To Make the First Decision
Return for Revision	2025-03-31 09:33
Revised	2025-04-13 15:56
Second Decision	2025-05-15 02:36
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-05-15 08:37
Articles in Press	2025-05-15 08:37
Publication Fee Transferred	2025-04-17 07:25
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1949-8462 (online)
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