| Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause nemaline myopathy with cores. | |
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MedLine Citation:
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PMID: 21109227 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We identified a member of the BTB/Kelch protein family that is mutated in nemaline myopathy type 6 (NEM6), an autosomal-dominant neuromuscular disorder characterized by the presence of nemaline rods and core lesions in the skeletal myofibers. Analysis of affected families allowed narrowing of the candidate region on chromosome 15q22.31, and mutation screening led to the identification of a previously uncharacterized gene, KBTBD13, coding for a hypothetical protein and containing missense mutations that perfectly cosegregate with nemaline myopathy in the studied families. KBTBD13 contains a BTB/POZ domain and five Kelch repeats and is expressed primarily in skeletal and cardiac muscle. The identified disease-associated mutations, C.742C>A (p.Arg248Ser), c.1170G>C (p.Lys390Asn), and c.1222C>T (p.Arg408Cys), located in conserved domains of Kelch repeats, are predicted to disrupt the molecule's beta-propeller blades. Previously identified BTB/POZ/Kelch-domain-containing proteins have been implicated in a broad variety of biological processes, including cytoskeleton modulation, regulation of gene transcription, ubiquitination, and myofibril assembly. The functional role of KBTBD13 in skeletal muscle and the pathogenesis of NEM6 are subjects for further studies. |
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Authors:
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Nyamkhishig Sambuughin; Kyle S Yau; Montse Olivé; Rachael M Duff; Munkhuu Bayarsaikhan; Shajia Lu; Laura Gonzalez-Mera; Padma Sivadorai; Kristen J Nowak; Gianina Ravenscroft; Frank L Mastaglia; Kathryn N North; Biljana Ilkovski; Hannie Kremer; Martin Lammens; Baziel G M van Engelen; Vicki Fabian; Phillipa Lamont; Mark R Davis; Nigel G Laing; Lev G Goldfarb |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2010-11-25 |
Journal Detail:
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Title: American journal of human genetics Volume: 87 ISSN: 1537-6605 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-07 Completed Date: 2011-01-18 Revised Date: 2011-07-29 |
Medline Journal Info:
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Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: United States |
Other Details:
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Languages: eng Pagination: 842-7 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Anesthesiology, Uniformed Services University, Bethesda, MD 20814, USA. nsambuughin@usuhs.mil |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Age of Onset Amino Acid Sequence Animals Child Chromosomes, Human, Pair 15 Genes, Dominant* Humans Immunohistochemistry Molecular Sequence Data Muscle Proteins / genetics* Mutation, Missense* Myopathies, Nemaline / genetics* Sequence Homology, Amino Acid |
| Chemical | |
Reg. No./Substance:
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0/KBTBD13 protein, human; 0/Muscle Proteins |
| Comments/Corrections | |
Erratum In:
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Am J Hum Genet. 2011 Jan 7;88(1):122 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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