Dataset Information

Comprehensive analysis for genetic diagnosis of Dystrophinopathies in Japan.

ABSTRACT: Duchenne muscular dystrophy (DMD) is the most common disease in children caused by mutations in the DMD gene, and DMD and Becker muscular dystrophy (BMD) are collectively called dystrophinopathies. Dystrophinopathies show a complex mutation spectrum. The importance of mutation databases, with clinical phenotypes and protein studies of patients, is increasingly recognized as a reference for genetic diagnosis and for the development of gene therapy.We used the data from the Japanese Registry of Muscular Dystrophy (Remudy) compiled during from July 2009 to March 2017, and reviewed 1497 patients with dystrophinopathies.The spectrum of identified mutations contained exon deletions (61%), exon duplications (13%), nonsense mutations (13%), small deletions (5%), small insertions (3%), splice-site mutations (4%), and missense mutations (1%). Exon deletions were found most frequently in the central hot spot region between exons 45-52 (42%), and most duplications were detected in the proximal hot spot region between exons 3-25 (47%). In the 371 patients harboring a small mutation, 194 mutations were reported and 187 mutations were unreported.We report the largest dystrophinopathies mutation dataset in Japan from a national patient registry, "Remudy". This dataset provides a useful reference to support the genetic diagnosis and treatment of dystrophinopathy.

SUBMITTER: Okubo M

PROVIDER: S-EPMC5580216 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Comprehensive analysis for genetic diagnosis of Dystrophinopathies in Japan.

Okubo Mariko M Goto Kanako K Komaki Hirofumi H Nakamura Harumasa H Mori-Yoshimura Madoka M Hayashi Yukiko K YK Mitsuhashi Satomi S Noguchi Satoru S Kimura En E Nishino Ichizo I

Orphanet journal of rare diseases 20170831 1

<h4>Background</h4>Duchenne muscular dystrophy (DMD) is the most common disease in children caused by mutations in the DMD gene, and DMD and Becker muscular dystrophy (BMD) are collectively called dystrophinopathies. Dystrophinopathies show a complex mutation spectrum. The importance of mutation databases, with clinical phenotypes and protein studies of patients, is increasingly recognized as a reference for genetic diagnosis and for the development of gene therapy.<h4>Methods</h4>We used the da ...[more]

PMID: 28859693

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Project description:BackgroundDystrophinopathies are a set of severe and incurable X-linked neuromuscular disorders caused by mutations in the dystrophin gene (DMD). These mutations form a complex spectrum. A national registration network is essential not only to provide more information about the prevalence and natural history of the disease, but also to collect genetic data for analyzing the mutational spectrum. This information is extremely beneficial for basic scientific research, genetic diagnosis, trial planning, clinical care, and gene therapy.MethodsWe collected data from 1400 patients (1042 patients with confirmed unrelated Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]) registered in the Chinese Genetic Disease Registry from March 2012 to August 2017 and analyzed the genetic mutational characteristics of these patients.ResultsLarge deletions were the most frequent type of mutation (72.2%), followed by nonsense mutations (11.9%), exon duplications (8.8%), small deletions (3.0%), splice-site mutations (2.1%), small insertions (1.3%), missense mutations (0.6%), and a combination mutation of a deletion and a duplication (0.1%). Exon 45-50 deletion was the most frequent deletion type, while exon 2 duplication was the most common duplication type. Two deletion hotspots were calculated-one located toward the central part (exon 45-52) of the gene and the other toward the 5'end (exon 8-26). We found no significant difference between hereditary and de novo mutations on deletion hotspots. Nonsense mutations accounted for 62.9% of all small mutations (197 patients).ConclusionWe built a comprehensive national dystrophinopathy mutation database in China, which is essential for basic and clinical research in this field. The mutational spectrum and characteristics of this DMD/BMD group were largely consistent with those in previous international DMD/BMD studies, with some differences. Based on our results, about 12% of DMD/BMD patients with nonsense mutations may benefit from stop codon read-through therapy. Additionally, the top three targets for exon-skipping therapy are exon 51 (141, 13.5%), exon 53 (115, 11.0%), and exon 45 (84, 8.0%).

Dataset Information

Comprehensive analysis for genetic diagnosis of Dystrophinopathies in Japan.

Publications

Comprehensive analysis for genetic diagnosis of Dystrophinopathies in Japan.

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