Ataxia-Telangiectasia with Novel Splicing Mutations in the ATM Gene
نویسندگان
چکیده
Heejeong Jeong, M.D.*, Hee Jae Huh, M.D.*, Jinyoung Youn, M.D., Ji Sun Kim, M.D., Jin Whan Cho, Ph.D., and Chang-Seok Ki, M.D. Department of Neurology, Gyeongsang National University School of Medicine, Jinju; Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology, Soonchunhyang University Hospital, Soonchunhyang University School of Medicine, Seoul, Korea
منابع مشابه
Dexamethasone partially rescues ataxia telangiectasia-mutated (ATM) deficiency in ataxia telangiectasia by promoting a shortened protein variant retaining kinase activity.
Ataxia telangiectasia (AT) is a rare genetic disease, still incurable, resulting from biallelic mutations in the ataxia telangiectasia-mutated (ATM) gene. Recently, short term treatment with glucocorticoid analogues improved neurological symptoms characteristic of this syndrome. Nevertheless, the molecular mechanism involved in glucocorticoid action in AT patients is not yet known. Here we desc...
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Mutations resulting in defective splicing constitute a significant proportion (30/62 [48%]) of a new series of mutations in the ATM gene in patients with ataxia-telangiectasia (AT) that were detected by the protein-truncation assay followed by sequence analysis of genomic DNA. Fewer than half of the splicing mutations involved the canonical AG splice-acceptor site or GT splice-donor site. A hig...
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We have previously reported a natural GTAA deletion within an intronic splicing processing element (ISPE) of the ataxia telangiectasia mutated (ATM) gene that disrupts a non-canonical U1 snRNP interaction and activates the excision of the upstream portion of the intron. The resulting pre-mRNA splicing intermediate is then processed to a cryptic exon, whose aberrant inclusion in the final mRNA i...
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Mutations in the ATM gene are responsible for the multisystem disorder ataxia-telangiectasia, characterized by neurodegeneration, immune deficiency and cancer predisposition. While no alternative splicing was identified within the coding region, the first four exons of the ATM gene, which fall within the 5'untranslated region (UTR), undergo extensive alternative splicing. We identified 12 diffe...
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Ataxia-telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder. It is characterized by early-onset, progressive cerebellar ataxia, oculomotor apraxia, choreoathetosis, conjunctival telangiectasias, immunodeficiency, and an increased risk of malignancy. Although A-T is known to be the most common cause of progressive cerebellar ataxia in childhood, there have been no confir...
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