کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3081352 1189372 2009 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Becker muscular dystrophy caused by an intronic mutation reducing the efficiency of the splice donor site of intron 26 of the dystrophin gene
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب تکاملی
پیش نمایش صفحه اول مقاله
Becker muscular dystrophy caused by an intronic mutation reducing the efficiency of the splice donor site of intron 26 of the dystrophin gene
چکیده انگلیسی
We describe an 11-year-old boy with dystrophinopathy who presented with a history of progressive proximal muscle weakness and elevated serum creatine kinase levels at age 6. Sequence analysis of the dystrophin (DMD) gene did not identify a mutation in the coding regions but revealed a nucleotide substitution in intron 26 (c.3603+3A>T). Since computer algorithms did not conclusively indicate that this sequence variant inactivated the splice site, we analyzed the DMD mRNA from a muscle biopsy of the patient to determine its functional significance. PCR and sequence analysis of the cDNA demonstrated that the mutation reduced the efficiency of the donor splice site and caused activation of a cryptic donor site 113 bp downstream. Activation of the cryptic donor site led to inclusion of 116 bp of intronic sequence containing a stop codon producing a truncated dystrophin protein. Residual wild-type splicing was also detected, which would explain the milder Becker rather than Duchenne phenotype in this patient. We highlight the importance of mRNA analysis for determination of pathogenicity in patients with ambiguous sequence variants in the DMD gene.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuromuscular Disorders - Volume 19, Issue 3, March 2009, Pages 189-192
نویسندگان
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