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.
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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.
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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
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DOI: https://doi.org/10.1038/ng1261
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