A Novel HRAS Mutation Independently Contributes to Left Ventricular Hypertrophy in a Family with a Known MYH7 MutationReportar como inadecuado




A Novel HRAS Mutation Independently Contributes to Left Ventricular Hypertrophy in a Family with a Known MYH7 Mutation - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Several genetic conditions can lead to left ventricular hypertrophy LVH. Among them, hypertrophic cardiomyopathy HCM, caused by mutations in sarcomere genes, is the most common inherited cardiac disease. Instead, RASopathies, a rare class of disorders characterized by neuro-cardio-facial-cutaneous abnormalities and sometimes presenting with LVH, are caused by mutations in the RAS-MAPK pathway. We report on a 62-years-old male who presented isolated severe obstructive LVH but did not carry the sarcomere mutation previously identified in his affected relatives. By exome sequencing, we detected a novel mutation in HRAS gene NM 005343.2:p.Arg68Trp, present also in the proband’s daughter, who showed mild LVH and severe intellectual disability. The cardiac phenotype was indistinguishable between family members carrying either mutation. In silico studies suggested that the mutated HRAS protein is constitutionally activated. Consistently, functional characterization in vitro confirmed elevated HRAS-GTP accumulation and downstream RAS-MAPK pathway activation that are known to drive cell proliferation in LVH. Our study emphasizes the role of RAS signaling in cardiac hypertrophy and highlights the complexity in differential diagnosis of RASopathies. In fact, the mild features of RASopathy and the recurrence of sarcomeric HCM in this family delayed the correct diagnosis until comprehensive genetic testing was performed.



Autor: Maria Elena Sana, Lawrence A. Quilliam, Andrea Spitaleri, Laura Pezzoli, Daniela Marchetti, Chiara Lodrini, Elisabetta Candiago,

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados