Dominant Mutations in KBTBD13, a Member of the BTB/Kelch Family, Cause Nemaline Myopathy with Cores
| Autor: | Kyle S. Yau, Nyamkhishig Sambuughin, Baziel G.M. van Engelen, Montse Olivé, Martin Lammens, Munkhuu Bayarsaikhan, Biljana Ilkovski, Frank L. Mastaglia, Rachael M. Duff, Shajia Lu, Vicki Fabian, Kristen J. Nowak, Phillipa J. Lamont, Padma Sivadorai, Gianina Ravenscroft, Kathryn N. North, Nigel G. Laing, Hannie Kremer, Mark R. Davis, Laura Gonzalez-Mera, Lev G. Goldfarb |
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| Rok vydání: | 2010 |
| Předmět: |
Myofibril assembly
Genetics and epigenetic pathways of disease [NCMLS 6] Molecular Sequence Data Mutation Missense Muscle Proteins Functional Neurogenomics Human Movement & Fatigue [DCN 2] Biology Myopathies Nemaline medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Nemaline myopathy Report Perception and Action [DCN 1] Genetics medicine Animals Humans Missense mutation Genetics(clinical) Amino Acid Sequence Age of Onset Child Nemaline bodies Kelch protein Genetics (clinical) Genes Dominant 030304 developmental biology Functional Neurogenomics Renal disorder [DCN 2] Chromosomes Human Pair 15 0303 health sciences Mutation Sequence Homology Amino Acid Gigaxonin medicine.disease Immunohistochemistry Congenital myopathy Genetics and epigenetic pathways of disease Functional Neurogenomics [NCMLS 6] Erratum Functional Neurogenomics [DCN 2] 030217 neurology & neurosurgery |
| Zdroj: | American Journal of Human Genetics, 87, 842-7 American Journal of Human Genetics, 87, 6, pp. 842-7 American Journal of Human Genetics, 87, 842-842 American Journal of Human Genetics, 87, pp. 842-842 |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2010.10.020 |
| Popis: | Contains fulltext : 88858.pdf (Publisher’s version ) (Closed access) 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. |
| Databáze: | OpenAIRE |
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