RAF1 mutation leading to hypertrophic cardiomyopathy in a Chinese family with a history of sudden cardiac death: A diagnostic insight into Noonan syndrome.

Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 101603758 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2324-9269 (Electronic) Linking ISSN: 23249269 NLM ISO Abbreviation: Mol Genet Genomic Med Subsets: MEDLINE

Original Publication: [Hoboken, NJ] : John Wiley & Sons, [2013]-

Cardiomyopathy, Hypertrophic*/diagnosis ; Cardiomyopathy, Hypertrophic*/genetics ; Noonan Syndrome*/diagnosis ; Noonan Syndrome*/genetics; Humans ; Young Adult ; China ; Death, Sudden, Cardiac/etiology ; Mutation ; Proto-Oncogene Proteins c-raf/genetics

Background: Hypertrophic cardiomyopathy (HCM) is predominantly caused by mutations in sarcomeric genes. However, a subset of cases is attributed to genetic disorders unrelated to sarcomeric genes, such as Noonan syndrome (NS) and other RASopathies. In this study, we present a family with a history of sudden cardiac death (SCD) and focus on two adults with syndromic left ventricular hypertrophy (LVH).
Methods: Clinical evaluations, including echocardiography, were conducted to assess cardiac manifestations. Whole-exome sequencing was performed to identify potential genetic variants underlying syndromic LVH in the study participants.
Results: Whole-exome sequencing revealed a missense variant in the RAF1 gene, c.782C>T (p.Pro261Leu). This variant confirmed the diagnosis of NS in the affected individuals.
Conclusion: The findings of this study underscore the importance of family history investigation and genetic testing in diagnosing syndromic LVH. By identifying the underlying genetic cause, clinicians can better understand the etiology of RAS-HCM and its association with SCD in young adults.
(© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

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81901919 National Natural Science Foundation of China; 81920108021 National Natural Science Foundation of China; 2020A1515010078 Natural Science Foundation of Guangdong Province

Keywords: Noonan syndrome; RAF1 gene; RAS-HCM; hypertrophic cardiomyopathy; whole-exome sequencing

EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
EC 2.7.11.1 (Raf1 protein, human)

Date Created: 20231003 Date Completed: 20240207 Latest Revision: 20240207

20240207

PMC10767430

10.1002/mgg3.2290

37787490