Elevation of serum creatine kinase as the only manifestation of an intragenic deletion of the dystrophin gene in three unrelated families

Comparative Analysis of Antisense Oligonucleotide Sequences for Targeted Skipping of Exon 51 During Dystrophin Pre-mRNA Splicing in Human Muscle

“…These revertant dystrophins lack exon domains flanking the gene lesion in DMD patients (Fanin et al, 1995;Thanh et al, 1995) and the mutated exon 23 in the mdx mouse (Lu et al, 2000). Despite being internally truncated, dystrophin molecules found in BMD patients can be functional, as demonstrated by several families with in-frame deletions in the DMD gene, associated with elevated serum creatine kinase but displaying no clinical myopathy (e.g., deletions of exons 32-44, 48-51, or 48-53 [Melis et al, 1998], exon 48 [Morrone et al, 1997], exons 48-51 or 50-53 [Beggs et al, 1991], exons 45-55 [Beroud et al, 2007], or exons 50-51 [Lesca et al, 2007]). The efficacy of internally truncated dystrophins lacking an appreciable portion of the rod domain has also been demonstrated in transgenic mdx mice, and exploited to design so-called microdystrophins compatible with delivery by AAV vectors.…”

Deletion of exon 16 of the dystrophin gene is not associated with disease

“…Deletions removing only the first part of the central rod domain have been found in almost asymptomatic individuals, in persons with elevated serum creatine kinase levels, and in patients suffering from muscle cramps upon exercise (Gospe, Jr. et al, 1989;Angelini et al, 1994;Ishigaki et al, 1996;Novakovic et al, 2005;artsma-Rus et al, 2006). Many of the more mildly affected patients have even large in-frame deletions in the central rod domain (England et al, 1990a;Yazaki et al, 1999), and patients with elevated or borderline CK as the only manifestations have also been reported (Melis et al, 1998). Thus this domain has been subject to extensive investigations using the transgenic mdx mouse as a model for DMD.…”

Clinical Utility Gene Card for: Becker muscular dystrophy

“…The difference in phenotype is usually dependent on whether the variant is in frame, resulting in an internally deleted, shorter, yet partially functional dystrophin protein (BMD), or out-offrame resulting in no dystrophin protein (DMD) [1]. However, other clinical phenotypes may arise from a DMD variant such as isolated quadriceps myopathy [2]; asymptomatic hyperCKemia [3]; myalgia, cramps and rhabdomyolysis [4]; dilated cardiomyopathy [5]; isolated cognitive impairment [6]; and symptomatic female carriers [7].…”

“…Below 100%. Some individuals with DMD variants are asymptomatic [39], or present with only slightly elevated serum CK levels and no other phenotype [3]. However, if the variant is known to cause BMD in family members, the index patient will almost certainly develop disease.…”