z-logo
Premium
Pseudoexon activation in the DMD gene as a novel mechanism for Becker muscular dystrophy
Author(s) -
TufferyGiraud Sylvie,
Saquet Céline,
Chambert Sylvie,
Claustres Mireille
Publication year - 2003
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10214
Subject(s) - exon , biology , muscular dystrophy , genetics , intron , duchenne muscular dystrophy , rna splicing , mutation , gene , dystrophin , microbiology and biotechnology , rna
We report the characterization of two deep intronic mutations in the Duchenne muscular dystrophy ( DMD ) gene of two unrelated Becker muscular dystrophy (BMD) patients, causing the aberrant inclusion of a pseudoexon in the mature transcripts. These two mutations were identified by the use of RT‐PCR on transcripts isolated from muscle. The first abnormally large transcript resulting from a 58‐bp insertion between exon 62 and exon 63 was identified in a BMD patient with mental retardation. The origin of this transcript was a mutation in intron 62 (IVS62–285A>G), which resulted in the occurrence of a high quality donor splice site. The IVS25+2036A>G in intron 25 was identified in a subclinical BMD patient with high CK levels. The mutation reinforces the strength of a pre‐existing acceptor splice site, resulting in activation of an intronic pseudoexon of 95 bp. By using DHPLC, the patient's mother was found to be a somatic mosaic. The insertion of these newly recognized extra exons leads to premature termination codons, but we could observe that some degree of normal splicing was taking place in both patients. The detection of these residual full length transcripts is consistent with the clinical presentation and dystrophin analyses. This is the first report of pseudoexon activation as a mechanism for Becker muscular dystrophy, and this reveals further the diversity of genetic abnormalities causing BMD. Hum Mutat 21:608–614, 2003. © 2003 Wiley‐Liss, Inc.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here