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The massive parallel sequencing: a useful genetic technology for the advance in the study of laminopathies

Fragmento de ADN
Thursday, November 22, 2018

Today more than 150 pathologies are known as neuromuscular ones (NMD), well a wide group of rare neurological disorders whose main feature is the loss of muscular force. These concern less than 1 for every 2,000 persons. NMD diseases are mostly congenital, that is to say, inherited from the parents. In this respect, its genetic nature is very varying and this implies that the standardization of clinical information records is still too basic to face up to the mentioned heterogeneity in developing therapeutic targets and defining health cares. 

The enhancing scientific knowledge on genetics opened the door towards understanding these ailments and the diagnoses started to begin more accurate. Nevertheless, there is still much work to be done, since in many typologies of NMD the genes responsible for neuromuscular degeneracy have not yet been well identified or, at best, the identified genes associated with these rare disorders are too much, and this means that exhaustive molecular diagnosis would be a too complex process. In recent years, one of the genetic technologies which more are leading to an advance in NMDs’ studies is the massive parallel sequencing (also called Next-Generation Sequencing – NGS). The application of this technology enables to achieve genetic simultaneous analyses of genes in a limited time and with a minor cost and detects variants of nucleotides and another type of mutations that up to the moment were very complicated to identify.    

Inside the NMDs there is a group of pathologies, the laminopathies, which are defined by the alteration in the gene LMNA, which codifies the protein lamin A/C. This protein belongs to the family of lamins, a type of protein which is essential for the maintenance of the structure of the cell nucleus. Actually, more than 500 pathogenic variants of the LMNA have been identified, which affect essentially the skeletal muscle, the cardiac one or to both in a simultaneous way. All that could end in cardiopathies and on occasions in sudden deaths before diagnosis. In order to improve the early diagnosis of these diseases, the Centre of Cardiovascular Genetics and the SJD Barcelona Children’s Hospital have designed and validated a panel of massive parallel sequencing that includes more than one hundred genes associated with neuromuscular pathologies. They could have analysed so far more than 25 families with some member affected by muscular dystrophy associated with LMNA, most of them children who also suffer from serious cardiac alterations. The project has already begun to give its results. In fact, different variants of the gene LMNA, as well as other genetic modifications, have already been identified. The results of this study will feed into the development of new lines of research in the diagnosis and treatment of the laminopathies and shall enable in the near future to launch personalised clinical trials.

Revista Genética Médica 


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