title: When a mid-intronic variation of DMD gene creates an ESE site.
abstract: 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.
authors.affiliation: Charles Nicolle Hospital, Congenital and Hereditary Diseases, Tunis, Tunisia; Faculty of Medicine, University Tunis El Manar, Tunisia. Electronic address: mediha_tr@yahoo.fr.
authors.forename: Madiha
authors.initials: M
authors.lastname: Trabelsi
authors.affiliation: Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Beugnet
authors.affiliation: Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Deburgrave
authors.affiliation: Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, Paris, France.
authors.forename: Virgine
authors.initials: V
authors.lastname: Commere
authors.affiliation: Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, Paris, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Orhant
authors.affiliation: Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, Paris, France.
authors.forename: France
authors.initials: F
authors.lastname: Leturcq
authors.affiliation: Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, Paris, France.
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
mesh_terms: D004252:DNA Mutational Analysis; D016189:Dystrophin / Q000235:genetics*; D005091:Exons; D006801:Humans; D007438:Introns; D008875:Middle Aged; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000503:physiopathology; D012326:RNA Splicing; D012333:RNA, Messenger
chemical_list: C484258:DMD protein, human; D016189:Dystrophin; D012333:RNA, Messenger
keywords: Becker muscular dystrophy; Dystrophin; ESE site; Mid-intronic variation