MLPA-based genotype–phenotype analysis in 1053 Chinese patients with DMD/BMD

Yang, Juan; Li, Shao Y; Li, Ya Q; Cao, Ji Q; Feng, Shan W; Wang, Yan Y; Zhan, Yi Xin; Yu, Chang Shun; Chen, Fei; Li, Jing; Sun, X F; Zhang, Cheng

doi:10.1186/1471-2350-14-29

Cited by 66 publications

(81 citation statements)

References 20 publications

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“…23 At present, some studies about DMD gene mutations of Chinese patients with DMD or BMD have been published. Juan Yang et al 24 used MLPA to detect the mutations in 1053 Chinese patients with DMD/BMD, 59.35 and 11.21% of which were deletions and duplications, respectively. However they concentrated more on the deletion and duplication mutations and only performed Sanger sequencing in 20 patients with negative MLPA.…”

Section: Discussionmentioning

confidence: 99%

DMD mutation spectrum analysis in 613 Chinese patients with dystrophinopathy

et al. 2015

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Dystrophinopathy is a group of inherited diseases caused by mutations in the DMD gene. Within the dystrophinopathy spectrum, Duchenne and Becker muscular dystrophies are common X-linked recessive disorders that mainly feature striated muscle necrosis. We combined multiplex ligation-dependent probe amplification with Sanger sequencing to detect large deletions/duplications and point mutations in the DMD gene in 613 Chinese patients. A total of 571 (93.1%) patients were diagnosed, including 428 (69.8%) with large deletions/duplications and 143 (23.3%) with point mutations. Deletion/duplication breakpoints gathered mostly in introns 44-55. Reading frame rules could explain 88.6% of deletion mutations. We identified seventy novel point mutations that had not been previously reported. Spectrum expansion and genotype-phenotype analysis of DMD mutations on such a large sample size in Han Chinese population would provide new insights into the pathogenic mechanism underlying dystrophinopathies.

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Section: Discussionmentioning

confidence: 99%

DMD mutation spectrum analysis in 613 Chinese patients with dystrophinopathy

et al. 2015

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“…Studies of mutation characteristics and the genotype-phenotype correlation have been performed in various countries 11. The present study is the first large-scale one aimed at identifying the MLPA-based genotype-phenotype correlation in an Indian population.…”

Section: Introductionmentioning

confidence: 99%

Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Confirmed by Multiplex Ligation-Dependent Probe Amplification: Genotype-Phenotype Correlation in a Large Cohort

et al. 2017

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Background and PurposeStudies of cases of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) confirmed by multiplex ligation-dependent probe amplification (MLPA) have determined the clinical characteristics, genotype, and relations between the reading frame and phenotype for different countries. This is the first such study from India.MethodsA retrospective genotype-phenotype analysis of 317 MLPA-confirmed patients with DMD or BMD who visited the neuromuscular clinic of a quaternary referral center in southern India.ResultsThe 317 patients comprised 279 cases of DMD (88%), 32 of BMD (10.1%), and 6 of intermediate phenotype (1.9%). Deletions accounted for 91.8% of cases, with duplications causing the remaining 8.2%. There were 254 cases of DMD (91%) with deletions and 25 (9%) due to duplications, and 31 cases (96.8%) of BMD with deletions and 1 (3.2%) due to duplication. All six cases of intermediate type were due to deletions. The most-common mutation was a single-exon deletion. Deletions of six or fewer exons constituted 68.8% of cases. The deletion of exon 50 was the most common. The reading-frame rule held in 90% of DMD and 94% of BMD cases. A tendency toward a lower IQ and earlier wheelchair dependence was observed with distal exon deletions, though a significant correlation was not found.ConclusionsThe reading-frame rule held in 90% to 94% of children, which is consistent with reports from other parts of the world. However, testing by MLPA is a limitation, and advanced sequencing methods including analysis of the structure of mutant dystrophin is needed for more-accurate assessments of the genotype-phenotype correlation.

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“…The skipping of one or more exons flanking the specific deletion site in patients with DMD allows for the introduction of BMD-like dystrophin and as a result, converts severe DMD into a BMDtype disease [15,16]. In this regard, gathering clinical and genetic information of patients with BMD has become more important for determining a precise genotype-phenotype correlation [14]. Because the phenotypic severity is different according to the deletion site in patients with BMD, exon-skipping therapies would also be affected by the specific site to be skipped.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, advances have been noted in the treatment of DMD by the development of exon skipping therapies [14]. The skipping of one or more exons flanking the specific deletion site in patients with DMD allows for the introduction of BMD-like dystrophin and as a result, converts severe DMD into a BMDtype disease [15,16].…”

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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MLPA-based genotype–phenotype analysis in 1053 Chinese patients with DMD/BMD

Cited by 66 publications

References 20 publications

DMD mutation spectrum analysis in 613 Chinese patients with dystrophinopathy

DMD mutation spectrum analysis in 613 Chinese patients with dystrophinopathy

Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Confirmed by Multiplex Ligation-Dependent Probe Amplification: Genotype-Phenotype Correlation in a Large Cohort

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

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