Document Detail

Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause nemaline myopathy with cores.
MedLine Citation:
PMID:  21109227     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2010-11-25
Journal Detail:
Title:  American journal of human genetics     Volume:  87     ISSN:  1537-6605     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-07     Completed Date:  2011-01-18     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  842-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Department of Anesthesiology, Uniformed Services University, Bethesda, MD 20814, USA.
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MeSH Terms
Age of Onset
Amino Acid Sequence
Chromosomes, Human, Pair 15
Genes, Dominant*
Molecular Sequence Data
Muscle Proteins / genetics*
Mutation, Missense*
Myopathies, Nemaline / genetics*
Sequence Homology, Amino Acid
Reg. No./Substance:
0/KBTBD13 protein, human; 0/Muscle Proteins
Erratum In:
Am J Hum Genet. 2011 Jan 7;88(1):122

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