Journal article
Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause nemaline myopathy with cores
The American Journal of Human Genetics, Vol.87(6), pp.842-847
2010
Abstract
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.
Details
- Title
- Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause nemaline myopathy with cores
- Authors/Creators
- N. Sambuughin (Author/Creator) - Uniformed Services University of the Health SciencesK.S. Yau (Author/Creator) - The University of Western AustraliaM. Olivé (Author/Creator) - Bellvitge University HospitalR.M. Duff (Author/Creator) - The University of Western AustraliaM. Bayarsaikhan (Author/Creator) - Uniformed Services University of the Health SciencesS. Lu (Author/Creator) - National Institute of Arthritis and Musculoskeletal and Skin DiseasesL. Gonzalez-Mera (Author/Creator) - Bellvitge University HospitalP. Sivadorai (Author/Creator) - Royal Perth HospitalK.J. Nowak (Author/Creator) - The University of Western AustraliaG. Ravenscroft (Author/Creator) - The University of Western AustraliaF.L. Mastaglia (Author/Creator) - The University of Western AustraliaK.N. North (Author/Creator) - Children's Hospital at WestmeadB. Ilkovski (Author/Creator) - Children's Hospital at WestmeadH. Kremer (Author/Creator) - Radboud University Medical CenterM. Lammens (Author/Creator) - Radboud University Medical CenterB.G.M. van Engelen (Author/Creator) - Radboud University Medical CenterV. Fabian (Author/Creator) - Royal Perth HospitalP. Lamont (Author/Creator) - Royal Perth HospitalM.R. Davis (Author/Creator) - Royal Perth HospitalN.G. Laing (Author/Creator) - The University of Western AustraliaL.G. Goldfarb (Author/Creator) - National Institute of Neurological Disorders and Stroke
- Publication Details
- The American Journal of Human Genetics, Vol.87(6), pp.842-847
- Publisher
- Elsevier Inc.
- Identifiers
- 991005542737207891
- Copyright
- © 2010 The American Society of Human Genetics.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.96 Cell Biology
- 1.96.492 Myosin
- Web Of Science research areas
- Genetics & Heredity
- ESI research areas
- Molecular Biology & Genetics