Clinical Characteristics of Aged Becker Muscular Dystrophy Patients with Onset after 30 Years

Yazaki, Masahide; Yoshida, Katsumi; Nakamura, Akinori; Koyama, Jun; Nanba, Takashi; Ohori, Nobuhira; Ikeda, Shu‐ichi

doi:10.1159/000008089

Cited by 62 publications

(42 citation statements)

References 13 publications

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“…9,10 The third patient revealed the mild BMD phenotype of late onset. 9,11 Our patients support the hypothesis that del45-55 could be a good candidate for the goal of a multiple exonskipping strategy for DMD.…”

Section: Introductionsupporting

confidence: 74%

“…[9][10][11] The patient number in this study corresponded to that in the previous report. 9 Patients 1 and 2 shared the similar clinical phenotype of XLDCM.…”

Section: Materials and Methods Patientsmentioning

confidence: 85%

“…Patient 3 showed the mild BMD phenotype with muscular atrophy and weakness in the extremities, which began around the age of 59 years. 9,11 He showed no obvious cardiac involvement.…”

Section: Materials and Methods Patientsmentioning

confidence: 98%

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Characterization of deletion breakpoints in patients with dystrophinopathy carrying a deletion of exons 45–55 of the Duchenne muscular dystrophy (DMD) gene

et al. 2009

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Deletion of exons 45-55 (del45-55) in the Duchenne muscular dystrophy gene (DMD) has gained particular interest in the field of molecular therapy, because it causes a milder phenotype than DMD, and therefore, may represent a good candidate for the goal of a multiple exon-skipping strategy. We have precisely characterized deletion breakpoints in three patients with del45-55 in DMD. Two of them were young adult males of the X-linked dilated cardiomyopathy phenotype, and the third patient revealed the mild Becker muscular dystrophy phenotype of late onset. The deletion breakpoints differed among patients. The deletion started at nt 226 604, 231 518, 117 284 in intron 44, and ended at nt 64 994, 59 314, 71 806 in intron 55, respectively. Deletion junctions showed no significant homology between the sequences adjacent to the distal and proximal end joints in these patients. Deletion breakpoints were not primarily associated with any particular sequence element, or with a matrix attachment region. However, there were several palindromic sequences and short tandem repeats at or near the breakpoints. These sequences, with a marked propensity to form secondary DNA structure intermediates, may predispose local DNA to breakage and intragenic recombination in these patients. Keywords: breakpoint; deletion; Duchenne muscular dystrophy (DMD); dystrophin; genomic sequence; X-linked dilated cardiomyopathy (XLDCM) INTRODUCTIONThe Duchenne muscular dystrophy gene (DMD) is the largest one so far identified, spanning more than 2.5 Mb and occupying roughly 0.1% of the human genome. 1 Mutations in DMD cause a devastating muscular dystrophy named Duchenne/Becker muscular dystrophy (DMD/BMD). The cardio-specific phenotype of dystrophinopathy is also known as X-linked dilated cardiomyopathy (XLDCM). 1 Intragenic deletions and duplications together account for over two-thirds of the mutations found in DMD/BMD patients. [2][3][4][5][6][7] Despite heterogeneity in both deletion size and location, two deletion 'hotspots' have been identified in DMD: a minor 'hotspot' including exons 2-19, and the major one involving exons 40-50 or 45-55. 2,4,5,7 Among deletions of variable sizes and locations found in DMD/ BMD patients, deletion of exons 45-55 (del45-55) in DMD has gained particular attention because an artificial dystrophin with del45-55 created by a multiple exon-skipping strategy could transform the DMD phenotype into the asymptomatic or milder BMD phenotype. 8 We reported three patients with del45-55 who presented with the phenotypes far from DMD. 9 Two of them were young adult males of the XLDCM phenotype. 9,10 The third patient revealed the mild BMD phenotype of late onset. 9,11 Our patients support the hypothesis that del45-55 could be a good candidate for the goal of a multiple exonskipping strategy for DMD.To elucidate the molecular basis of del45-55 in more detail, we have characterized the breakpoints of del45-55 in DMD in these three patients. To our knowledge, only two breakpoints have been precisely described in intron 44,...

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Section: Introductionsupporting

confidence: 74%

“…[9][10][11] The patient number in this study corresponded to that in the previous report. 9 Patients 1 and 2 shared the similar clinical phenotype of XLDCM.…”

Section: Materials and Methods Patientsmentioning

confidence: 85%

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Characterization of deletion breakpoints in patients with dystrophinopathy carrying a deletion of exons 45–55 of the Duchenne muscular dystrophy (DMD) gene

et al. 2009

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“…The average age of symptom onset is 12 years old, but there is significant variability. Severity can range from a DMD-like presentation to mild weakness and exercise intolerance presenting in the 6 th decade (Yazaki, 1999). Almost 90% of affected individuals are symptomatic by age 20 years .…”

Section: Clinical Featuresmentioning

confidence: 99%

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy

et al. 2014

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Introduction: Disease inclusion in the newborn screening (NBS) panel should consider the opinions of those most affected by the outcome of screening. We assessed the level and factors that affect parent attitudes regarding NBS panel inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and spinal muscular atrophy (SMA). Methods: The attitudes toward NBS for DMD, BMD, and SMA were surveyed and compared for 2 categories of parents, those with children affected with DMD, BMD, or SMA and expectant parents unselected for known family medical history. Results: The level of support for NBS for DMD, BMD, and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among expectant parents. Conclusions: There was strong support for NBS for DMD, BMD, and SMA in both groups of parents. Given advances in diagnostics and promising therapeutic approaches, discussion of inclusion in NBS should continue. Muscle Nerve 49: 822–828, 2014

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“…Some of the patients with BMD are asymptomatic while others become wheelchair-bound around 16 years of age. The patients could survive until very old ages or some of them could die from an early heart failure [8,9]. Although the underlying mechanism of this variability is not fully understood, it is likely that both levels and functionality of the internally deleted dystrophins play a significant role [10].…”

Section: Discussionmentioning

confidence: 99%

Identification of two novel Duchenne muscular dystrophies mutations in patients with Becker muscular dystrophy

Kim

Seo

et al. 2017

J Genet Med

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JGMand may have near normal lives [2,3].The differential diagnosis of BMD and DMD in suspected cases is based on their clinical findings, muscle biopsy, and the mutations in DMD. Among these, positive staining for dystrophin in muscle biopsies is an important finding in the differential diagnosis [4,5]. However, since muscle biopsies are invasive procedures, the differential diagnosis of BMD and DMD is often dependent on the mutations in DMD gene identified in the patient. According to the mutation database or previous reports, each DMD mutation is classified as either a DMD-or BMDcausing mutation [6]. However, when a novel DMD mutation is identified, the differential diagnosis should be based on the muscle biopsy findings along with other clinical findings. IntroductionDuchenne and Becker muscular dystrophies (DMD, OMIM #310200 and BMD, OMIM #300376; respectively) are caused by mutations in DMD, the dystrophin-coding gene. These conditions are inherited in an X-linked recessive manner with a prevalence of 1 in 4,000 to 5,000 new born males [1].DMD and BMD are characterized by progressive muscular weakness. DMD is a severely disabling neuromuscular disease that leads to premature death of patients at approximately 19 years of age due to cardiac or respiratory failure. In contrast, BMD is a milder form with a later onset and slower rate of progression, and patients older than 16 years remain ambulatory www.e-kjgm.org Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are X-linked neuromuscular disorders characterized by progressive muscle weakness and severe skeletal muscle degeneration. BMD is a milder form with a later onset. Patients with BMD tend to survive much longer than those with DMD. The differentiation between DMD and BMD is important in the genetic counseling of affected patients and their families. Since muscle biopsies are invasive procedures, the differential diagnosis of BMD and DMD is often dependent on the mutation identified in the DMD gene in affected patients. However, when a novel DMD mutation is identified, the differential diagnosis should be based on muscle biopsy findings with other clinical findings. Here we describe two Korean patients with BMD confirmed by muscle biopsy and genetic testing. Two novel exonic deletions in the DMD gene were identified.

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Clinical Characteristics of Aged Becker Muscular Dystrophy Patients with Onset after 30 Years

Cited by 62 publications

References 13 publications

Characterization of deletion breakpoints in patients with dystrophinopathy carrying a deletion of exons 45–55 of the Duchenne muscular dystrophy (DMD) gene

Characterization of deletion breakpoints in patients with dystrophinopathy carrying a deletion of exons 45–55 of the Duchenne muscular dystrophy (DMD) gene

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy

Identification of two novel Duchenne muscular dystrophies mutations in patients with Becker muscular dystrophy

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