RNA-seq analysis, targeted long-read sequencing and in silico prediction to unravel pathogenic intronic events and complicated splicing abnormalities in dystrophinopathy
| العنوان: | RNA-seq analysis, targeted long-read sequencing and in silico prediction to unravel pathogenic intronic events and complicated splicing abnormalities in dystrophinopathy |
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| المؤلفون: | Mariko Okubo, Satoru Noguchi, Tomonari Awaya, Motoyasu Hosokawa, Nobue Tsukui, Megumu Ogawa, Shinichiro Hayashi, Hirofumi Komaki, Madoka Mori-Yoshimura, Yasushi Oya, Yuji Takahashi, Tetsuhiro Fukuyama, Michinori Funato, Yousuke Hosokawa, Satoru Kinoshita, Tsuyoshi Matsumura, Sadao Nakamura, Azusa Oshiro, Hiroshi Terashima, Tetsuro Nagasawa, Tatsuharu Sato, Yumi Shimada, Yasuko Tokita, Masatoshi Hagiwara, Katsuhisa Ogata, Ichizo Nishino |
| المساهمون: | National Center of Neurology and Psychiatry National Institute of Mental Health (NCNP), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), National Center of Neurology and Psychiatry [Tokyo, Japan], Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, National Center of Neurology and Psychiatry, Department of neurology, The University of Tokyo (UTokyo), Toneyama National Hospital |
| المصدر: | Human Genetics Human Genetics, 2022, ⟨10.1007/s00439-022-02485-2⟩ |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio], Genetics, Genetics (clinical) |
| الوصف: | Dystrophinopathy is caused by alterations in DMD. Approximately 1% of patients remain genetically undiagnosed, because intronic variations are not detected by standard methods. Here, we combined laboratory and in silico analyses to identify disease-causing genomic variants in genetically undiagnosed patients and determine the regulatory mechanisms underlying abnormal DMD transcript generation. DMD transcripts from 20 genetically undiagnosed dystrophinopathy patients in whom no exon variants were identified, despite dystrophin deficiency on muscle biopsy, were analyzed by transcriptome sequencing. Genome sequencing captured intronic variants and their effects were interpreted using in silico tools. Targeted long-read sequencing was applied in cases with suspected structural genomic abnormalities. Abnormal DMD transcripts were detected in 19 of 20 cases; Exonization of intronic sequences in 15 cases, exon skipping in one case, aberrantly spliced and polyadenylated transcripts in two cases and transcription termination in one case. Intronic single nucleotide variants, chromosomal rearrangements and nucleotide repeat expansion were identified in DMD gene as pathogenic causes of transcript alteration. Our combined analysis approach successfully identified pathogenic events. Detection of diseasing-causing mechanisms in DMD transcripts could inform the therapeutic options for patients with dystrophinopathy. |
| تدمد: | 1432-1203 0340-6717 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d4311749a28528eab6bb5d5989835c8 https://pubmed.ncbi.nlm.nih.gov/36048237 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....8d4311749a28528eab6bb5d5989835c8 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14321203 03406717 |
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