• Spanish scientists identify a gene whose mutations cause cardiac alterations and familial sudden death

    October 29, 2014

    The research has been based on the use of new techniques of sequencing and analysis of the human genome

    From left to right, Carlos López-Otín, José Julián Reguero, Eliecer Coto, Rafael Valdés Mas, Juan Gómez, Ana Gutiérrez Fernández, Diana Álvarez Puente, and Xose Puente.

    A study based on the sequencing of the genome of Spanish patients of hypertrophic myocardiopathy has led to the identification of a new familial form of this disease and to the discovery of the mutated gen that causes its development. This research, published today by the prestigious journal Nature Communications, provides a new light on the molecular alterations in charge of a disease that causes numerous cases of sudden death.

    The research has been directed by Doctors Carlos López-Otín and Xose S. Puente of the Institute of Oncology of the University of Oviedo, and has had the participation of the groups led by Doctors Eliecer Coto, José Julián R. Reguero and Aurora Astudillo of the Central University Hospital of Asturias.

    Hypertrophic Myocardiopathy is a relatively-frequent disease that represents one of the main causes of suddent death in young adults. In recent years, the study of family cases of this disease has led to the discovery of diverse genes that cause its development in approximately 50% of the patients, although the genes responsible for hypertrophic myocardiopathy in the rest of the patients are still completely unknown.

    "This dramatic reality encouraged us to study the genome of families with cases of sudden death, using the new techniques of genomic analysis developed in our laboratory as part of the project to decypher the genomes of cancer", explains Dr. Carlos López-Otín, Tenured Professor of Biochemistry and Molecular Biology of the University of Oviedo, and director of the Spanish contribution to the International Consortium of Cancer Genomes. "The genomic study has allowed us to precise which mutations on the FLNC gene, which codifies a protein called filamin C, cause hypertrophic myocardiopathy in 8 of the families studied", says Dr. Xosé S. Puente.

    After discovering these mutations, the research team analyzed the underlying mechanisms of the development of the disease, which has allowed them to prove that "mutations on FLNC cause the formation of masses of proteins in the cardiac muscle that accumulate over time and prevent the correct functioning of the heart", comment Rafel Valdés and Ana Gutiérrez-Fernandez, first signers of the article of Nature Communications.

    This discovery has important and immediate clinical applications, since, according to Drs. Coto and Reguero, "it will allow us to provide genetic counseling in families and to identify the carriers of mutations on FLNC, who will be under constant clinical survelliance and, if necessary, will be given a defibrilator that prevents the process that triggers sudden death".

    The work conducted by the Institutions participating in this project is funded by the Ministry of Economics and Competitiveness, the Carlos III Health Institute, the Cajastur Social Work, the Botín Foundation and the Asturcor Foundation.


    Rafael Valdés-Mas, Ana Gutiérrez-Fernández, Juan Gómez, Eliecer Coto, Aurora Astudillo, Diana A. Puente, Julián R. Reguero, Victoria Alvarez, César Moris, Diego León, María Martín, Xose S. Puente, Carlos López-Otín. "Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy" Nature Commun (2014) DOI: 10.1038/ncomms6326

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    Figure that represents a cardiac cell with a mass of mutant filamin C (in green).