ORIGINAL RESEARCH

Analysis of phenotype expressions of deletions in the dystrophin gene in terms of efficiency of exon skipping as a method for treatment of hereditary dystrophinopathies

About authors

1 Marlin Biotech, Moscow, Russia

2 Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia

3 Department of Neurology, Neurosurgery and Medical Genetics, Medical Faculty,
Pirogov Russian National Research Medical University, Moscow, Russia

Correspondence should be addressed: Evgeniya Zotova
ul. Vavilova, d.34/5, Moscow, Russia, 119334; ur.usm.bbf@avotoz

About paper

Acknowledgements: authors thank the Shared Resource Center of the Institute of Gene Biology of Russian Academy of Sciences for the equipment provided for this research.

Received: 2016-06-17 Accepted: 2016-06-24 Published online: 2017-01-05
|

Duchenne muscular dystrophy (DMD) is a common genetic disease caused by a mutation of the dystrophin gene. It leads to death in childhood. At the time of writing this paper, patients had access to supportive therapy only. However, DMD treatment methods are actively being developed. Exon skipping is a promising method. Exon skipping involves restoration of the reading frame within a gene by inducing alternative splicing. This leads to synthesis of truncated but still functional dystrophin. The paper assesses the functionality of the truncated forms of dystrophin resulting from correction of nonsense mutations and internal exon indels by exon-skipping technique. The assessment was made based on data on the phenotype of carriers of mutations in the dystrophin gene taken from the Leiden Open Variation Database (LOVD). It was revealed that the same mutation could manifest itself as a variety of phenotypes. This, perhaps, is as a result of the patients having different genetic background. For example, deletion of exon 48, for which there is 97 records in LOVD, resulted in asymptomatic diseases in 2 % of cases, Duchenne muscular dystrophy in 60 %, Becker muscular dystrophy (characterized by milder symptoms than DMD) in 12 % and intermediate phenotype in 26 % of cases. High phenotypic variability of mutations of the dystrophin gene raises the issue of limits of applying exon skipping for treatment of inherited myopathies.

Keywords: Duchenne muscular dystrophy, muscular dystrophy, Becker muscular dystrophy, exon skipping

КОММЕНТАРИИ (1)