| Functional assessment of TSC1 missense variants identified in individuals with tuberous sclerosis complex. | |
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MedLine Citation:
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PMID: 22161988 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 or TSC2 genes. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a complex that inhibits the mammalian target of rapamycin (mTOR) complex 1 (TORC1). Previously, we demonstrated that pathogenic amino acid substitutions in the N-terminal domain of TSC1 (amino acids 50-224) are destabilising. Here we investigate an additional 21 unclassified TSC1 variants. Our functional assessment identified 4 substitutions (p.L61R, p.G132D, p.F158S and p.R204P) between amino acids 50 and 224 that reduced TSC1 stability and prevented the TSC1-TSC2-dependent inhibition of TORC1. In 4 cases (20%) our functional assessment did not agree with the predictions of the SIFT amino acid substitution analysis software. Our new data confirm our previous finding that the N-terminal region of TSC1 is essential for TSC1 function. |
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Authors:
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Marianne Hoogeveen-Westerveld; Rosemary Ekong; Sue Povey; Izabela Karbassi; Sat Dev Batish; Johan T den Dunnen; Agnies van Eeghen; Elizabeth Thiele; Karin Mayer; Kira Dies; Li Wen; Catherine Thompson; Steven P Sparagana; Peter Davies; Cora Aalfs; Ans van den Ouweland; Dicky Halley; Mark Nellist |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-12 |
Journal Detail:
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Title: Human mutation Volume: - ISSN: 1098-1004 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9215429 Medline TA: Hum Mutat Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 Wiley Periodicals, Inc. |
Affiliation:
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Department of Clinical Genetics, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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