Recurrent Dominant Mutations Affecting Two Adjacent Residues in the Motor Domain of the Monomeric Kinesin KIF22 Result in Skeletal Dysplasia and Joint Laxity
| Autor: | Sebastian Kalamajski, H. Rosemarie Davidson, A. Belinda Campos-Xavier, Eugênia Ribeiro Valadares, Goranka Tanackovich, Andrea Superti-Furga, Christine Hall, Daniel H. Cohn, Massimiliano Rossi, Generoso Andria, R. Curtis Rogers, Shiro Ikegawa, Diana Ballhausen, André Mégarbané, Michael D. Briggs, Sheila Unger, David L. Rimoin, Claire L. Hartley, Rainer König, Richard H Scott, Luisa Bonafé, Ralph S. Lachman, Eric D. Boyden, John F. Bateman, Pierre-Simon Jouk, Geert Mortier, Philippe Suarez, Trevor L. Cameron, Matthew L. Warman, Hirotake Sawada, Gen Nishimura |
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| Přispěvatelé: | Boyden, Ed, Campos Xavier, Ab, Kalamajski, S, Cameron, Tl, Suarez, P, Tanackovic, G, Andria, Generoso, Ballhausen, D, Briggs, Md, Hartley, C, Cohn, Dh, Davidson, Hr, Hall, C, Ikegawa, S, Jouk, P, König, R, Megarbané, A, Nishimura, G, Lachman, R, Mortier, G, Rimoin, Dl, Rogers, Rc, Rossi, M, Sawada, H, Scott, R, Unger, S, Valadares, Er, Bateman, Jf, Warman, Ml, Superti Furga, A, Bonafé, L., Tanackovich, G |
| Rok vydání: | 2011 |
| Předmět: |
Male
Joint Dislocations Gene Expression Kinesins Joint laxity Motor domain Mice 0302 clinical medicine Missense mutation Exome Genetics(clinical) Growth Plate Child Cells Cultured Genetics (clinical) Genes Dominant Genetics 0303 health sciences Chemistry Joint Laxity Monomeric Kinesin KIF22 Phenotype Cell biology DNA-Binding Proteins Kinesin Erratum Joint Instability Skeletal Dysplasia Mutation Missense Biology Osteochondrodysplasias 03 medical and health sciences Skeletal disorder Report medicine Animals Humans Abnormalities Multiple Amino Acid Sequence Genetic Association Studies 030304 developmental biology Spondyloepimetaphyseal dysplasia Base Sequence Tibia Sequence Analysis DNA medicine.disease Protein Structure Tertiary Dysplasia Human medicine 030217 neurology & neurosurgery |
| Zdroj: | American journal of human genetics The American journal of human genetics |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2011.10.016 |
| Popis: | 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 beyond those previously ascribed functions involving chromosome segregation. Although we have found Kif22 to be strongly upregulated at the growth plate, the precise pathogenetic mechanisms remain to be elucidated. |
| Databáze: | OpenAIRE |
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