Abstract
Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Engle, E.C. et al. Ann. Neurol. 41, 314–325 (1997).
Engle, E.C., Kunkel, L.M., Specht, L.A. & Beggs, A.H. Nat. Genet. 7, 69–73 (1994).
Engle, E.C. et al. Am. J. Hum. Genet. 57, 1086–1094 (1995).
Engle, E.C. et al. BMC Genet. 3, 3 (2002).
Uyama, E. et al. Neuromuscul. Disord. 13, 472–478 (2003).
Marszalek, J.R., Weiner, J.A., Farlow, S.J., Chun, J. & Goldstein, L.S. J. Cell. Biol. 145, 469–479 (1999).
Doherty, E. et al. Invest. Ophthalmol. Vis. Sci. 40, 1687–1694 (1999).
Mackey, D.A. et al. Hum. Genet. 110, 510–512 (2002).
Miki, H., Setou, M., Kaneshiro, K. & Hirokawa, N. Proc. Natl. Acad. Sci. USA 98, 7004–7011 (2001).
Peretti, D., Peris, L., Rosso, S., Quiroga, S. & Caceres, A. J. Cell. Biol. 149, 141–152 (2000).
Zhao, C. et al. Cell 105, 587–597 (2001).
Reid, E. et al. Am. J. Hum. Genet. 71, 1189–1194 (2002).
Magli, A., De Berardinis, T., D'Esposito, F. & Gagliardi, V. BMC Ophthalmol. 3, 6 (2003).
Harley, R.D., Rodrigues, M.M. & Crawford, J.S. J. Pediatr. Ophthalmol. Strabismus 15, 346–358 (1978).
Brodsky, M. Ophthalmology 105, 717–725 (1998).
Acknowledgements
We thank all the participants in this study; J.H. Calhoun, R. Baker, E. Ballard, G. Rogers and R. Fellows for pedigree referrals; J. Scharf and A. Beggs for critically reading this manuscript; K. Miura and R.R. Bennett for advice and suggestions; M.P. Rogines-Velo-Sardi and C. Miranda for discussion; and C. St Hilaire for technical assistance. This work was supported by grants from the US National Institutes of Health and by the Children's Hospital Mental Retardation Research Center.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Rights and permissions
About this article
Cite this article
Yamada, K., Andrews, C., Chan, WM. et al. Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Nat Genet 35, 318–321 (2003). https://doi.org/10.1038/ng1261
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ng1261
This article is cited by
-
Regulation of ciliary homeostasis by intraflagellar transport-independent kinesins
Cell Death & Disease (2024)
-
MRI evaluation of cranial nerve abnormalities and extraocular muscle fibrosis in duane retraction syndrome and congenital extraocular muscle fibrosis
Graefe's Archive for Clinical and Experimental Ophthalmology (2024)
-
Differential splicing of neuronal genes in a Trem2*R47H mouse model mimics alterations associated with Alzheimer’s disease
BMC Genomics (2023)
-
Kif21a deficiency leads to impaired glomerular filtration barrier function
Scientific Reports (2023)
-
Phenotype, genotype, and management of congenital fibrosis of extraocular muscles type 1 in 16 Chinese families
Graefe's Archive for Clinical and Experimental Ophthalmology (2023)
