Journal article
Recurrent dominant mutations affecting two adjacent residues in the motor domain of the monomeric kinesin KIF22 result in skeletal dysplasia and joint laxity
ED Boyden, AB Campos-Xavier, S Kalamajski, TL Cameron, P Suarez, G Tanackovich, G Andria, D Ballhausen, MD Briggs, C Hartley, DH Cohn, HR Davidson, C Hall, S Ikegawa, PS Jouk, R König, A Megarbané, G Nishimura, RS Lachman, G Mortier Show all
American Journal of Human Genetics | CELL PRESS | Published : 2011
Abstract
Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto-SEMDJL, aka SEMDJL, Hall type), is an autosomal dominant skeletal disorder that, in spite of being relatively common among skeletal dysplasias, has eluded molecular elucidation so far. We used whole-exome sequencing of five unrelated individuals with lepto-SEMDJL to identify mutations in KIF22 as the cause of this skeletal condition. Missense mutations affecting one of two adjacent amino acids in the motor domain of KIF22 were present in 20 familial cases from eight families and in 12 other sporadic cases. The skeletal and connective tissue phenotype produced by these specific mutations point to functions of KIF22 ..
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Awarded by Eunice Kennedy Shriver National Institute of Child Health and Human Development
Funding Acknowledgements
This work was supported by the Howard Hughes Medical Institute, by the Swiss National Research Foundation, grant 310030_132940 to L.B., by the National Institutes of Health grant HD22657 to D.H.C., and by the National Health and Medical Research Council of Australia, Project grant 607398 to J.F.B. and the Victorian Government's Operational Infrastructure Support Program. A.S.F. is supported by the Leenaards Foundation (Lausanne, Switzerland) and by the Faculty of Biology and Medicine of the Lausanne University (Fonds de Recherche en Pediatrie). We thank the staff of the Harvard Medical School Biopolymers Facility for assistance in exome sequencing. We are grateful to S. Miyagawa, Department of Pediatrics, Kure Medical Center, Japan, for collaboration in sample collection.