The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Identification of KLHL41 Mutations Implicates BTB-Kelch-Mediated Ubiquitination as an Alternate Pathway to Myofibrillar Disruption in Nemaline Myopathy
Open accessAbstract
Nemaline myopathy (NM) is a rare congenital muscle disorder primarily affecting skeletal muscles that results in neonatal death in severe cases as a result of associated respiratory insufficiency. NM is thought to be a disease of sarcomeric thin filaments as six of eight known genes whose mutation can cause NM encode components of that structure, however, recent discoveries of mutations in non-thin filament genes has called this model in question. We performed whole-exome sequencing and have identified recessive small deletions and missense changes in the Kelch-like family member 41 gene (KLHL41) in four individuals from unrelated NM families. Sanger sequencing of 116 unrelated individuals with NM identified compound heterozygous changes in KLHL41 in a fifth family. Mutations in KLHL41 showed a clear phenotype-genotype correlation: Frameshift mutations resulted in severe phenotypes with neonatal death, whereas missense changes resulted in impaired motor function with survival into late childhood and/or early adulthood. Functional studies in zebrafish showed that loss of Klhl41 results in highly diminished motor function and myofibrillar disorganization, with nemaline body formation, the pathological hallmark of NM. These studies expand the genetic heterogeneity of NM and implicate a critical role of BTB-Kelch family members in maintenance of sarcomeric integrity in NM.
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“which have a documented role in the biology of nemaline myopathy146,147.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [146]
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Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
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Mutations in the skeletal muscle α-actin gene in patients with actin myopathy and nemaline myopathy
Nowak, K. J., Wattanasirichaigoon, D., Goebel, H. H., Wilce, M. C. J., Pelin, K., Donner, K. M., Jacob, R. L., Hübner, C., Oexle, K., Anderson, J. R., et al. (1999) · Nature Genetics · doi:10.1038/13837 · Cited by 408
Self-citationA mutation in the α tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy
Laing, N. G., Wilton, S. D., Akkari, P. A., Dorosz, S. M., Boundy, K. L., Kneebone, C., Blumbergs, P. C., White, S. J., Watkins, H. C., Love, D. R., et al. (1995) · Nature Genetics · doi:10.1038/ng0195-75 · Cited by 356
Self-citationMutations in the nebulin gene associated with autosomal recessive nemaline myopathy
Pelin, K., Hotulainen, P., Donner, K. M., Sewry, C. A., Akkari, P. A., Wilton, S. D., Wattanasirichaigoon, D., Bang, M., Centner, T., Hanefeld, F. A., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2305 · Cited by 336
Self-citationA Novel Nemaline Myopathy in the Amish Caused by a Mutation in Troponin T1
Johnston, J. J., Kelley, R. I., Crawford, T. O., Morton, D. H., Agarwala, R., Koch, T., Schäffer, A. A., Francomano, C. A., & Biesecker, L. G. (2000) · The American Journal of Human Genetics · doi:10.1086/303089 · Cited by 328
Zhang, D. D., Lo, S., Sun, Z., Habib, G. M., Lieberman, M. W., & Hannink, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501279200 · Cited by 299
Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases
Canning, P., Cooper, C. D. O., Krojer, T., Murray, J. W., Pike, A. C. W., Chaikuad, A., Keates, T., Thangaratnarajah, C., Hojzan, V., Marsden, B. D., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.437996 · Cited by 284
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Self-citationUbiquitin ligases: guardians of mammalian development
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Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy
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Metadata
- Authors
- Gupta, V. A., Ravenscroft, G., Shaheen, R., Todd, E. J., Swanson, L. C., Shiina, M., Ogata, K., Hsu, C., Clarke, N. F., Darras, B. T., Farrar, M. A., Hashem, A., Manton, N. D., Muntoni, F., North, K. N., Sandaradura, S. A., Nishino, I., Hayashi, Y. K., Sewry, C. A., Thompson, E. M., Yau, K. S., Brownstein, C. A., Yu, T. W., Allcock, R. J. N., Davis, M. R., Wallgren-Pettersson, C., Matsumoto, N., Alkuraya, F. S., Laing, N. G., & Beggs, A. H.
- Affiliations
- Boston Children's Hospital (US)
- The University of Western Australia (AU)
- King Faisal Specialist Hospital & Research Centre (SA)
- Yokohama City University (JP)
- The University of Sydney (AU)
- Sydney Children's Hospital (AU)
- South Australia Pathology (AU)
- Royal Children's Hospital (AU)
- National Center of Neurology and Psychiatry (JP)
- Great Ormond Street Hospital (GB)
- Royal Perth Hospital (AU)
- Corresponding author
- Beggs, Alan H.
- ORCID
- Gupta, Vandana A.
- Ravenscroft, Gianina
- Shaheen, Ranad
- Shiina, Masaaki
- Ogata, Kazuhiro
- Darras, Basil T.
- Farrar, Michelle A.
- North, Kathryn N.
- Sandaradura, Sarah A.
- Nishino, Ichizo
- Hayashi, Yukiko K.
- Sewry, Caroline A.
- Brownstein, Catherine A.
- Yu, Timothy W.
- Davis, Mark R.
- Matsumoto, Naomichi
- Alkuraya, Fowzan S.
- Laing, Nigel G.
- Beggs, Alan H.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 93
- Issue
- 6
- Pages
- 1108-1117
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC3852928
- OpenAlex
- W1973202003
- Cited by
- 168
- References
- 35
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 12 · 2023: 8 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 15 · 2018: 22 · 2017: 12 · 2016: 16 · 2015: 16 · 2014: 23
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Muscular Dystrophy Association (MDA 201302)
- Rosetrees Trust
- Great Ormond Street Hospital Charity
- National Institutes of Health (HD18655)
- Medical Research Council (MR/K000608/1)
- National Health and Medical Research Council (1022707, 1002147, 1035955)
- Japan Society for the Promotion of Science (24118005, 24249019)
- National Heart, Lung, and Blood Institute
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01AR062601, R01AR044345)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- nemaline myopathy, ubiquitination, myofibrillar disorganization, nemaline bodies, genetic heterogeneity, compound heterozygosity, frameshift mutation, missense mutations, zebrafish model, motor function, congenital muscle disease
- MeSH terms
- Adolescent, Animals, Child, Child, Preschool, Cytoskeletal Proteins, Female, Humans, Infant, Infant, Newborn, Male, Models, Molecular, Mutation, Myofibrils, Protein Conformation, Proteins, Zebrafish, Signal Transduction, Gene Expression, Myopathies, Nemaline, Fatal Outcome, Muscle, Skeletal, Gene Order, Protein Interaction Domains and Motifs, Ubiquitination, Genetic Association Studies
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