Trabelsi Madiha, Beugnet Caroline, Deburgrave Nathalie, Commere Virgine, Orhant Lucie, Leturcq France, Chelly Jamel
Charles Nicolle Hospital, Congenital and Hereditary Diseases, Tunis, Tunisia; Faculty of Medicine, University Tunis El Manar, Tunisia.
Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, Paris, France.
Neuromuscul Disord. 2014 Dec;24(12):1111-7. doi: 10.1016/j.nmd.2014.07.003. Epub 2014 Aug 1.
Duchenne and Becker muscular dystrophy are X-linked allelic disorders caused by mutations in the DMD gene. The majority (65%) of these mutations are intragenic deletions/duplications that often lead to frameshift errors. Among the remaining ones, we find the mid-intronic mutations that usually create cryptic exons by activating potential splice sites. In this report, we identified, in a Becker muscular dystrophy patient, a mid-intronic variation that creates two ESE sites in intron 26 of DMD gene resulting in the insertion of a new cryptic exon in mRNA. Despite the out of frame character of this mutation, we observed the production of a reduced amount of full-size dystrophin which could be explained by the alternation between normal and altered splicing of dystrophin mRNA in this patient. To our knowledge, this is the first case report describing this novel pathogenic mechanism of mid-intronic variations of DMD gene.
杜兴氏和贝克氏肌营养不良症是由DMD基因突变引起的X连锁等位基因疾病。这些突变中的大多数（65%）是基因内缺失/重复，通常会导致移码错误。在其余的突变中，我们发现内含子中部突变通常通过激活潜在的剪接位点产生隐匿外显子。在本报告中，我们在一名贝克氏肌营养不良症患者中鉴定出一种内含子中部变异，该变异在DMD基因的第26内含子中产生了两个外显子增强子位点，导致mRNA中插入了一个新的隐匿外显子。尽管该突变具有移码特征，但我们观察到产生了少量的全长抗肌萎缩蛋白，这可以通过该患者抗肌萎缩蛋白mRNA正常剪接和异常剪接之间的交替来解释。据我们所知，这是第一例描述DMD基因内含子中部变异这种新致病机制的病例报告。
