Recurrent Dominant Mutations Affecting Two Adjacent Residues in the Motor Domain of the Monomeric Kinesin KIF22 Result in Skeletal Dysplasia and Joint Laxity
Identifieur interne : 001676 ( PascalFrancis/Corpus ); précédent : 001675; suivant : 001677Recurrent Dominant Mutations Affecting Two Adjacent Residues in the Motor Domain of the Monomeric Kinesin KIF22 Result in Skeletal Dysplasia and Joint Laxity
Auteurs : Eric D. Boyden ; A. Belinda Campos-Xavier ; Sebastian Kalamajski ; Trevor L. Cameron ; Philippe Suarez ; Goranka Tanackovich ; Generoso Andria ; Diana Ballhausen ; Michael D. Briggs ; Claire Hartley ; Daniel H. Cohn ; H. Rosemarie Davidson ; Christine Hall ; Shiro Ikegawa ; Pierre-Simon Jouk ; Rainer König ; Andre Megarbane ; Gen Nishimura ; Ralph S. Lachman ; Geert Mortier ; David L. Rimoin ; R. Curtis Rogers ; Massimiliano Rossi ; Hirotake Sawada ; Richard Scott ; Sheila Unger ; Eugenia Ribeiro Valadares ; John F. Bateman ; Matthew L. Warman ; Andrea Superti-Furga ; Luisa BonafeSource :
- American journal of human genetics [ 0002-9297 ] ; 2011.
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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 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.
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Format Inist (serveur)
| NO : | PASCAL 12-0043068 INIST |
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| ET : | Recurrent Dominant Mutations Affecting Two Adjacent Residues in the Motor Domain of the Monomeric Kinesin KIF22 Result in Skeletal Dysplasia and Joint Laxity |
| AU : | BOYDEN (Eric D.); CAMPOS-XAVIER (A. Belinda); KALAMAJSKI (Sebastian); CAMERON (Trevor L.); SUAREZ (Philippe); TANACKOVICH (Goranka); ANDRIA (Generoso); BALLHAUSEN (Diana); BRIGGS (Michael D.); HARTLEY (Claire); COHN (Daniel H.); ROSEMARIE DAVIDSON (H.); HALL (Christine); IKEGAWA (Shiro); JOUK (Pierre-Simon); KÖNIG (Rainer); MEGARBANE (Andre); NISHIMURA (Gen); LACHMAN (Ralph S.); MORTIER (Geert); RIMOIN (David L.); CURTIS ROGERS (R.); ROSSI (Massimiliano); SAWADA (Hirotake); SCOTT (Richard); UNGER (Sheila); RIBEIRO VALADARES (Eugenia); BATEMAN (John F.); WARMAN (Matthew L.); SUPERTI-FURGA (Andrea); BONAFE (Luisa) |
| AF : | Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School/Boston, MA 02115/Etats-Unis (1 aut., 3 aut., 29 aut.); Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois/1011 Lausanne/Suisse (2 aut., 5 aut., 8 aut., 30 aut., 31 aut.); Murdoch Childrens Research Institute/Parkville, Victoria 3052/Australie (4 aut., 28 aut.); Department of Medical Genetics, University of Lausanne/1011 Lausanne/Suisse (6 aut.); Department of Pediatrics, Federico II University/80131 Naples/Italie (7 aut., 23 aut.); Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester/Manchester M13 9PT/Royaume-Uni (9 aut., 10 aut.); Departments of Molecular, Cell and Developmental Biology and Orthopaedic Surgery, University of California, Los Angeles (UCLA)/Los Angeles, CA 90048/Etats-Unis (11 aut.); Ferguson Smith Centre for Clinical Genetics, Yorkhill Hospitals/Glasgow G3 8SJ/Royaume-Uni (12 aut.); Radiology Department, Institute of Child Health, Great Ormond Street Hospital/London WC1N 3JH/Royaume-Uni (13 aut.); Laboratory for Bone and Joint Diseases, Center for Genomic Medicine/Riken, Tokyo 108-8639/Japon (14 aut.); Clinical Genetics, Department of Genetics and Procreation, Centre Hospitalier Universitaire/38043 Grenoble/France (15 aut.); Institute of Human Genetics, Johann Wolfgang Goethe University Hospital/60590 Frankfurt/Main/Allemagne (16 aut.); Unité de Genetique médicale et Laboratoire associe Institut National de la Sante et de la Recherche Medicale, Universite Saint-Joseph, 11-5076 Riad El Solh/Beyrouth/Liban (17 aut.); Department of Radiology and Medical Imaging, Tokyo Metropolitan Children's Medical Center/Fuchu, Tokyo 183-8561/Japon (18 aut.); Medical Genetics Institute, Cedars-Sinai Medical Center/Los Angeles, CA 90048/Etats-Unis (19 aut., 21 aut.); Department of Medical Genetics, University Hospital of Antwerp, University of Antwerp/2650 Edegem/Belgique (20 aut.); Departments of Human Genetics, Pediatrics and Medicine, David Geffen School of Medicine at UCLA/Los Angeles, CA 90095-7088/Etats-Unis (21 aut.); Greenwood Genetic Center/Greenville, SC 29605/Etats-Unis (22 aut.); Department of Pediatrics, Miyazaki Medical College, University of Miyazaki, 5200 Kihara/Miyazaki 889-1692/Japon (24 aut.); Clinical Genetics, Great Ormond Street Hospital/London WC1N 3JH/Royaume-Uni (25 aut.); Department of Medical Genetics, Centre Hospitalier Universitaire Vaudois/1011 Lausanne/Suisse (26 aut.); Laboratory and Clinic for Inborn Errors Of Metabolism, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte/Minas Gerais 30130100/Brésil (27 aut.); Department of Biochemistry and Molecular Biology, University of Melbourne/Parkville, Victoria 3052/Australie (28 aut.) |
| DT : | Publication en série; Compte-rendu; Niveau analytique |
| SO : | American journal of human genetics; ISSN 0002-9297; Coden AJHGAG; Etats-Unis; Da. 2011; Vol. 89; No. 6; Pp. 767-772; Bibl. 34 ref. |
| LA : | Anglais |
| EA : | 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. |
| CC : | 002A04; 002A07; 002B23A |
| FD : | Dysplasie; Récidive; Récidivant; Caractère dominant; Mutation; Kinésine; Os; Squelette; Articulation; Hyperlaxité; Génétique; Homme |
| ED : | Dysplasia; Relapse; Recurrent; Dominant character; Mutation; Kinesin; Bone; Skeleton; Joint; Laxity; Genetics; Human |
| SD : | Displasia; Recaida; Recidivante; Carácter dominante; Mutación; Kinesina; Hueso; Esqueleto; Articulación; Hiperlaxitud; Genética; Hombre |
| LO : | INIST-2610.354000505975750080 |
| ID : | 12-0043068 |
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Pascal:12-0043068Le document en format XML
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Belinda Campos-Xavier</name><affiliation><inist:fA14 i1="02"><s1>Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ><sZ>30 aut.</sZ><sZ>31 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Kalamajski, Sebastian" sort="Kalamajski, Sebastian" uniqKey="Kalamajski S" first="Sebastian" last="Kalamajski">Sebastian Kalamajski</name><affiliation><inist:fA14 i1="01"><s1>Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School</s1><s2>Boston, MA 02115</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>29 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Cameron, Trevor L" sort="Cameron, Trevor L" uniqKey="Cameron T" first="Trevor L." last="Cameron">Trevor L. 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Briggs</name><affiliation><inist:fA14 i1="06"><s1>Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester</s1><s2>Manchester M13 9PT</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hartley, Claire" sort="Hartley, Claire" uniqKey="Hartley C" first="Claire" last="Hartley">Claire Hartley</name><affiliation><inist:fA14 i1="06"><s1>Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester</s1><s2>Manchester M13 9PT</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Cohn, Daniel H" sort="Cohn, Daniel H" uniqKey="Cohn D" first="Daniel H." last="Cohn">Daniel H. Cohn</name><affiliation><inist:fA14 i1="07"><s1>Departments of Molecular, Cell and Developmental Biology and Orthopaedic Surgery, University of California, Los Angeles (UCLA)</s1><s2>Los Angeles, CA 90048</s2><s3>USA</s3><sZ>11 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Rosemarie Davidson, H" sort="Rosemarie Davidson, H" uniqKey="Rosemarie Davidson H" first="H." last="Rosemarie Davidson">H. Rosemarie Davidson</name><affiliation><inist:fA14 i1="08"><s1>Ferguson Smith Centre for Clinical Genetics, Yorkhill Hospitals</s1><s2>Glasgow G3 8SJ</s2><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hall, Christine" sort="Hall, Christine" uniqKey="Hall C" first="Christine" last="Hall">Christine Hall</name><affiliation><inist:fA14 i1="09"><s1>Radiology Department, Institute of Child Health, Great Ormond Street Hospital</s1><s2>London WC1N 3JH</s2><s3>GBR</s3><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ikegawa, Shiro" sort="Ikegawa, Shiro" uniqKey="Ikegawa S" first="Shiro" last="Ikegawa">Shiro Ikegawa</name><affiliation><inist:fA14 i1="10"><s1>Laboratory for Bone and Joint Diseases, Center for Genomic Medicine</s1><s2>Riken, Tokyo 108-8639</s2><s3>JPN</s3><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Jouk, Pierre Simon" sort="Jouk, Pierre Simon" uniqKey="Jouk P" first="Pierre-Simon" last="Jouk">Pierre-Simon Jouk</name><affiliation><inist:fA14 i1="11"><s1>Clinical Genetics, Department of Genetics and Procreation, Centre Hospitalier Universitaire</s1><s2>38043 Grenoble</s2><s3>FRA</s3><sZ>15 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Konig, Rainer" sort="Konig, Rainer" uniqKey="Konig R" first="Rainer" last="König">Rainer König</name><affiliation><inist:fA14 i1="12"><s1>Institute of Human Genetics, Johann Wolfgang Goethe University Hospital</s1><s2>60590 Frankfurt/Main</s2><s3>DEU</s3><sZ>16 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Megarbane, Andre" sort="Megarbane, Andre" uniqKey="Megarbane A" first="Andre" last="Megarbane">Andre Megarbane</name><affiliation><inist:fA14 i1="13"><s1>Unité de Genetique médicale et Laboratoire associe Institut National de la Sante et de la Recherche Medicale, Universite Saint-Joseph, 11-5076 Riad El Solh</s1><s2>Beyrouth</s2><s3>LBN</s3><sZ>17 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Nishimura, Gen" sort="Nishimura, Gen" uniqKey="Nishimura G" first="Gen" last="Nishimura">Gen Nishimura</name><affiliation><inist:fA14 i1="14"><s1>Department of Radiology and Medical Imaging, Tokyo Metropolitan Children's Medical Center</s1><s2>Fuchu, Tokyo 183-8561</s2><s3>JPN</s3><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Lachman, Ralph S" sort="Lachman, Ralph S" uniqKey="Lachman R" first="Ralph S." last="Lachman">Ralph S. Lachman</name><affiliation><inist:fA14 i1="15"><s1>Medical Genetics Institute, Cedars-Sinai Medical Center</s1><s2>Los Angeles, CA 90048</s2><s3>USA</s3><sZ>19 aut.</sZ><sZ>21 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Mortier, Geert" sort="Mortier, Geert" uniqKey="Mortier G" first="Geert" last="Mortier">Geert Mortier</name><affiliation><inist:fA14 i1="16"><s1>Department of Medical Genetics, University Hospital of Antwerp, University of Antwerp</s1><s2>2650 Edegem</s2><s3>BEL</s3><sZ>20 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Rimoin, David L" sort="Rimoin, David L" uniqKey="Rimoin D" first="David L." last="Rimoin">David L. Rimoin</name><affiliation><inist:fA14 i1="15"><s1>Medical Genetics Institute, Cedars-Sinai Medical Center</s1><s2>Los Angeles, CA 90048</s2><s3>USA</s3><sZ>19 aut.</sZ><sZ>21 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="17"><s1>Departments of Human Genetics, Pediatrics and Medicine, David Geffen School of Medicine at UCLA</s1><s2>Los Angeles, CA 90095-7088</s2><s3>USA</s3><sZ>21 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Curtis Rogers, R" sort="Curtis Rogers, R" uniqKey="Curtis Rogers R" first="R." last="Curtis Rogers">R. Curtis Rogers</name><affiliation><inist:fA14 i1="18"><s1>Greenwood Genetic Center</s1><s2>Greenville, SC 29605</s2><s3>USA</s3><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Rossi, Massimiliano" sort="Rossi, Massimiliano" uniqKey="Rossi M" first="Massimiliano" last="Rossi">Massimiliano Rossi</name><affiliation><inist:fA14 i1="05"><s1>Department of Pediatrics, Federico II University</s1><s2>80131 Naples</s2><s3>ITA</s3><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sawada, Hirotake" sort="Sawada, Hirotake" uniqKey="Sawada H" first="Hirotake" last="Sawada">Hirotake Sawada</name><affiliation><inist:fA14 i1="19"><s1>Department of Pediatrics, Miyazaki Medical College, University of Miyazaki, 5200 Kihara</s1><s2>Miyazaki 889-1692</s2><s3>JPN</s3><sZ>24 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Scott, Richard" sort="Scott, Richard" uniqKey="Scott R" first="Richard" last="Scott">Richard Scott</name><affiliation><inist:fA14 i1="20"><s1>Clinical Genetics, Great Ormond Street Hospital</s1><s2>London WC1N 3JH</s2><s3>GBR</s3><sZ>25 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Unger, Sheila" sort="Unger, Sheila" uniqKey="Unger S" first="Sheila" last="Unger">Sheila Unger</name><affiliation><inist:fA14 i1="21"><s1>Department of Medical Genetics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>26 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ribeiro Valadares, Eugenia" sort="Ribeiro Valadares, Eugenia" uniqKey="Ribeiro Valadares E" first="Eugenia" last="Ribeiro Valadares">Eugenia Ribeiro Valadares</name><affiliation><inist:fA14 i1="22"><s1>Laboratory and Clinic for Inborn Errors Of Metabolism, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte</s1><s2>Minas Gerais 30130100</s2><s3>BRA</s3><sZ>27 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Bateman, John F" sort="Bateman, John F" uniqKey="Bateman J" first="John F." last="Bateman">John F. Bateman</name><affiliation><inist:fA14 i1="03"><s1>Murdoch Childrens Research Institute</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="23"><s1>Department of Biochemistry and Molecular Biology, University of Melbourne</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>28 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Warman, Matthew L" sort="Warman, Matthew L" uniqKey="Warman M" first="Matthew L." last="Warman">Matthew L. Warman</name><affiliation><inist:fA14 i1="01"><s1>Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School</s1><s2>Boston, MA 02115</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>29 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Superti Furga, Andrea" sort="Superti Furga, Andrea" uniqKey="Superti Furga A" first="Andrea" last="Superti-Furga">Andrea Superti-Furga</name><affiliation><inist:fA14 i1="02"><s1>Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ><sZ>30 aut.</sZ><sZ>31 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Bonafe, Luisa" sort="Bonafe, Luisa" uniqKey="Bonafe L" first="Luisa" last="Bonafe">Luisa Bonafe</name><affiliation><inist:fA14 i1="02"><s1>Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ><sZ>30 aut.</sZ><sZ>31 aut.</sZ></inist:fA14></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0043068</idno><date when="2011">2011</date><idno type="stanalyst">PASCAL 12-0043068 INIST</idno><idno type="RBID">Pascal:12-0043068</idno><idno type="wicri:Area/PascalFrancis/Corpus">001676</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Recurrent Dominant Mutations Affecting Two Adjacent Residues in the Motor Domain of the Monomeric Kinesin KIF22 Result in Skeletal Dysplasia and Joint Laxity</title><author><name sortKey="Boyden, Eric D" sort="Boyden, Eric D" uniqKey="Boyden E" first="Eric D." last="Boyden">Eric D. Boyden</name><affiliation><inist:fA14 i1="01"><s1>Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School</s1><s2>Boston, MA 02115</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>29 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Campos Xavier, A Belinda" sort="Campos Xavier, A Belinda" uniqKey="Campos Xavier A" first="A. Belinda" last="Campos-Xavier">A. Belinda Campos-Xavier</name><affiliation><inist:fA14 i1="02"><s1>Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ><sZ>30 aut.</sZ><sZ>31 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Kalamajski, Sebastian" sort="Kalamajski, Sebastian" uniqKey="Kalamajski S" first="Sebastian" last="Kalamajski">Sebastian Kalamajski</name><affiliation><inist:fA14 i1="01"><s1>Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School</s1><s2>Boston, MA 02115</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>29 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Cameron, Trevor L" sort="Cameron, Trevor L" uniqKey="Cameron T" first="Trevor L." last="Cameron">Trevor L. Cameron</name><affiliation><inist:fA14 i1="03"><s1>Murdoch Childrens Research Institute</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Suarez, Philippe" sort="Suarez, Philippe" uniqKey="Suarez P" first="Philippe" last="Suarez">Philippe Suarez</name><affiliation><inist:fA14 i1="02"><s1>Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ><sZ>30 aut.</sZ><sZ>31 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Tanackovich, Goranka" sort="Tanackovich, Goranka" uniqKey="Tanackovich G" first="Goranka" last="Tanackovich">Goranka Tanackovich</name><affiliation><inist:fA14 i1="04"><s1>Department of Medical Genetics, University of Lausanne</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>6 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Andria, Generoso" sort="Andria, Generoso" uniqKey="Andria G" first="Generoso" last="Andria">Generoso Andria</name><affiliation><inist:fA14 i1="05"><s1>Department of Pediatrics, Federico II University</s1><s2>80131 Naples</s2><s3>ITA</s3><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ballhausen, Diana" sort="Ballhausen, Diana" uniqKey="Ballhausen D" first="Diana" last="Ballhausen">Diana Ballhausen</name><affiliation><inist:fA14 i1="02"><s1>Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ><sZ>30 aut.</sZ><sZ>31 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Briggs, Michael D" sort="Briggs, Michael D" uniqKey="Briggs M" first="Michael D." last="Briggs">Michael D. Briggs</name><affiliation><inist:fA14 i1="06"><s1>Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester</s1><s2>Manchester M13 9PT</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hartley, Claire" sort="Hartley, Claire" uniqKey="Hartley C" first="Claire" last="Hartley">Claire Hartley</name><affiliation><inist:fA14 i1="06"><s1>Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester</s1><s2>Manchester M13 9PT</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Cohn, Daniel H" sort="Cohn, Daniel H" uniqKey="Cohn D" first="Daniel H." last="Cohn">Daniel H. Cohn</name><affiliation><inist:fA14 i1="07"><s1>Departments of Molecular, Cell and Developmental Biology and Orthopaedic Surgery, University of California, Los Angeles (UCLA)</s1><s2>Los Angeles, CA 90048</s2><s3>USA</s3><sZ>11 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Rosemarie Davidson, H" sort="Rosemarie Davidson, H" uniqKey="Rosemarie Davidson H" first="H." last="Rosemarie Davidson">H. Rosemarie Davidson</name><affiliation><inist:fA14 i1="08"><s1>Ferguson Smith Centre for Clinical Genetics, Yorkhill Hospitals</s1><s2>Glasgow G3 8SJ</s2><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hall, Christine" sort="Hall, Christine" uniqKey="Hall C" first="Christine" last="Hall">Christine Hall</name><affiliation><inist:fA14 i1="09"><s1>Radiology Department, Institute of Child Health, Great Ormond Street Hospital</s1><s2>London WC1N 3JH</s2><s3>GBR</s3><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ikegawa, Shiro" sort="Ikegawa, Shiro" uniqKey="Ikegawa S" first="Shiro" last="Ikegawa">Shiro Ikegawa</name><affiliation><inist:fA14 i1="10"><s1>Laboratory for Bone and Joint Diseases, Center for Genomic Medicine</s1><s2>Riken, Tokyo 108-8639</s2><s3>JPN</s3><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Jouk, Pierre Simon" sort="Jouk, Pierre Simon" uniqKey="Jouk P" first="Pierre-Simon" last="Jouk">Pierre-Simon Jouk</name><affiliation><inist:fA14 i1="11"><s1>Clinical Genetics, Department of Genetics and Procreation, Centre Hospitalier Universitaire</s1><s2>38043 Grenoble</s2><s3>FRA</s3><sZ>15 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Konig, Rainer" sort="Konig, Rainer" uniqKey="Konig R" first="Rainer" last="König">Rainer König</name><affiliation><inist:fA14 i1="12"><s1>Institute of Human Genetics, Johann Wolfgang Goethe University Hospital</s1><s2>60590 Frankfurt/Main</s2><s3>DEU</s3><sZ>16 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Megarbane, Andre" sort="Megarbane, Andre" uniqKey="Megarbane A" first="Andre" last="Megarbane">Andre Megarbane</name><affiliation><inist:fA14 i1="13"><s1>Unité de Genetique médicale et Laboratoire associe Institut National de la Sante et de la Recherche Medicale, Universite Saint-Joseph, 11-5076 Riad El Solh</s1><s2>Beyrouth</s2><s3>LBN</s3><sZ>17 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Nishimura, Gen" sort="Nishimura, Gen" uniqKey="Nishimura G" first="Gen" last="Nishimura">Gen Nishimura</name><affiliation><inist:fA14 i1="14"><s1>Department of Radiology and Medical Imaging, Tokyo Metropolitan Children's Medical Center</s1><s2>Fuchu, Tokyo 183-8561</s2><s3>JPN</s3><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Lachman, Ralph S" sort="Lachman, Ralph S" uniqKey="Lachman R" first="Ralph S." last="Lachman">Ralph S. Lachman</name><affiliation><inist:fA14 i1="15"><s1>Medical Genetics Institute, Cedars-Sinai Medical Center</s1><s2>Los Angeles, CA 90048</s2><s3>USA</s3><sZ>19 aut.</sZ><sZ>21 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Mortier, Geert" sort="Mortier, Geert" uniqKey="Mortier G" first="Geert" last="Mortier">Geert Mortier</name><affiliation><inist:fA14 i1="16"><s1>Department of Medical Genetics, University Hospital of Antwerp, University of Antwerp</s1><s2>2650 Edegem</s2><s3>BEL</s3><sZ>20 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Rimoin, David L" sort="Rimoin, David L" uniqKey="Rimoin D" first="David L." last="Rimoin">David L. Rimoin</name><affiliation><inist:fA14 i1="15"><s1>Medical Genetics Institute, Cedars-Sinai Medical Center</s1><s2>Los Angeles, CA 90048</s2><s3>USA</s3><sZ>19 aut.</sZ><sZ>21 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="17"><s1>Departments of Human Genetics, Pediatrics and Medicine, David Geffen School of Medicine at UCLA</s1><s2>Los Angeles, CA 90095-7088</s2><s3>USA</s3><sZ>21 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Curtis Rogers, R" sort="Curtis Rogers, R" uniqKey="Curtis Rogers R" first="R." last="Curtis Rogers">R. Curtis Rogers</name><affiliation><inist:fA14 i1="18"><s1>Greenwood Genetic Center</s1><s2>Greenville, SC 29605</s2><s3>USA</s3><sZ>22 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Rossi, Massimiliano" sort="Rossi, Massimiliano" uniqKey="Rossi M" first="Massimiliano" last="Rossi">Massimiliano Rossi</name><affiliation><inist:fA14 i1="05"><s1>Department of Pediatrics, Federico II University</s1><s2>80131 Naples</s2><s3>ITA</s3><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sawada, Hirotake" sort="Sawada, Hirotake" uniqKey="Sawada H" first="Hirotake" last="Sawada">Hirotake Sawada</name><affiliation><inist:fA14 i1="19"><s1>Department of Pediatrics, Miyazaki Medical College, University of Miyazaki, 5200 Kihara</s1><s2>Miyazaki 889-1692</s2><s3>JPN</s3><sZ>24 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Scott, Richard" sort="Scott, Richard" uniqKey="Scott R" first="Richard" last="Scott">Richard Scott</name><affiliation><inist:fA14 i1="20"><s1>Clinical Genetics, Great Ormond Street Hospital</s1><s2>London WC1N 3JH</s2><s3>GBR</s3><sZ>25 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Unger, Sheila" sort="Unger, Sheila" uniqKey="Unger S" first="Sheila" last="Unger">Sheila Unger</name><affiliation><inist:fA14 i1="21"><s1>Department of Medical Genetics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>26 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ribeiro Valadares, Eugenia" sort="Ribeiro Valadares, Eugenia" uniqKey="Ribeiro Valadares E" first="Eugenia" last="Ribeiro Valadares">Eugenia Ribeiro Valadares</name><affiliation><inist:fA14 i1="22"><s1>Laboratory and Clinic for Inborn Errors Of Metabolism, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte</s1><s2>Minas Gerais 30130100</s2><s3>BRA</s3><sZ>27 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Bateman, John F" sort="Bateman, John F" uniqKey="Bateman J" first="John F." last="Bateman">John F. Bateman</name><affiliation><inist:fA14 i1="03"><s1>Murdoch Childrens Research Institute</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="23"><s1>Department of Biochemistry and Molecular Biology, University of Melbourne</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>28 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Warman, Matthew L" sort="Warman, Matthew L" uniqKey="Warman M" first="Matthew L." last="Warman">Matthew L. Warman</name><affiliation><inist:fA14 i1="01"><s1>Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School</s1><s2>Boston, MA 02115</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>29 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Superti Furga, Andrea" sort="Superti Furga, Andrea" uniqKey="Superti Furga A" first="Andrea" last="Superti-Furga">Andrea Superti-Furga</name><affiliation><inist:fA14 i1="02"><s1>Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ><sZ>30 aut.</sZ><sZ>31 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Bonafe, Luisa" sort="Bonafe, Luisa" uniqKey="Bonafe L" first="Luisa" last="Bonafe">Luisa Bonafe</name><affiliation><inist:fA14 i1="02"><s1>Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ><sZ>30 aut.</sZ><sZ>31 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">American journal of human genetics</title><title level="j" type="abbreviated">Am. j. hum. genet.</title><idno type="ISSN">0002-9297</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">American journal of human genetics</title><title level="j" type="abbreviated">Am. j. hum. genet.</title><idno type="ISSN">0002-9297</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Bone</term><term>Dominant character</term><term>Dysplasia</term><term>Genetics</term><term>Human</term><term>Joint</term><term>Kinesin</term><term>Laxity</term><term>Mutation</term><term>Recurrent</term><term>Relapse</term><term>Skeleton</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Dysplasie</term><term>Récidive</term><term>Récidivant</term><term>Caractère dominant</term><term>Mutation</term><term>Kinésine</term><term>Os</term><term>Squelette</term><term>Articulation</term><term>Hyperlaxité</term><term>Génétique</term><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0002-9297</s0></fA01><fA02 i1="01"><s0>AJHGAG</s0></fA02><fA03 i2="1"><s0>Am. j. hum. genet.</s0></fA03><fA05><s2>89</s2></fA05><fA06><s2>6</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Recurrent Dominant Mutations Affecting Two Adjacent Residues in the Motor Domain of the Monomeric Kinesin KIF22 Result in Skeletal Dysplasia and Joint Laxity</s1></fA08><fA11 i1="01" i2="1"><s1>BOYDEN (Eric D.)</s1></fA11><fA11 i1="02" i2="1"><s1>CAMPOS-XAVIER (A. Belinda)</s1></fA11><fA11 i1="03" i2="1"><s1>KALAMAJSKI (Sebastian)</s1></fA11><fA11 i1="04" i2="1"><s1>CAMERON (Trevor L.)</s1></fA11><fA11 i1="05" i2="1"><s1>SUAREZ (Philippe)</s1></fA11><fA11 i1="06" i2="1"><s1>TANACKOVICH (Goranka)</s1></fA11><fA11 i1="07" i2="1"><s1>ANDRIA (Generoso)</s1></fA11><fA11 i1="08" i2="1"><s1>BALLHAUSEN (Diana)</s1></fA11><fA11 i1="09" i2="1"><s1>BRIGGS (Michael D.)</s1></fA11><fA11 i1="10" i2="1"><s1>HARTLEY (Claire)</s1></fA11><fA11 i1="11" i2="1"><s1>COHN (Daniel H.)</s1></fA11><fA11 i1="12" i2="1"><s1>ROSEMARIE DAVIDSON (H.)</s1></fA11><fA11 i1="13" i2="1"><s1>HALL (Christine)</s1></fA11><fA11 i1="14" i2="1"><s1>IKEGAWA (Shiro)</s1></fA11><fA11 i1="15" i2="1"><s1>JOUK (Pierre-Simon)</s1></fA11><fA11 i1="16" i2="1"><s1>KÖNIG (Rainer)</s1></fA11><fA11 i1="17" i2="1"><s1>MEGARBANE (Andre)</s1></fA11><fA11 i1="18" i2="1"><s1>NISHIMURA (Gen)</s1></fA11><fA11 i1="19" i2="1"><s1>LACHMAN (Ralph S.)</s1></fA11><fA11 i1="20" i2="1"><s1>MORTIER (Geert)</s1></fA11><fA11 i1="21" i2="1"><s1>RIMOIN (David L.)</s1></fA11><fA11 i1="22" i2="1"><s1>CURTIS ROGERS (R.)</s1></fA11><fA11 i1="23" i2="1"><s1>ROSSI (Massimiliano)</s1></fA11><fA11 i1="24" i2="1"><s1>SAWADA (Hirotake)</s1></fA11><fA11 i1="25" i2="1"><s1>SCOTT (Richard)</s1></fA11><fA11 i1="26" i2="1"><s1>UNGER (Sheila)</s1></fA11><fA11 i1="27" i2="1"><s1>RIBEIRO VALADARES (Eugenia)</s1></fA11><fA11 i1="28" i2="1"><s1>BATEMAN (John F.)</s1></fA11><fA11 i1="29" i2="1"><s1>WARMAN (Matthew L.)</s1></fA11><fA11 i1="30" i2="1"><s1>SUPERTI-FURGA (Andrea)</s1></fA11><fA11 i1="31" i2="1"><s1>BONAFE (Luisa)</s1></fA11><fA14 i1="01"><s1>Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School</s1><s2>Boston, MA 02115</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>29 aut.</sZ></fA14><fA14 i1="02"><s1>Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ><sZ>30 aut.</sZ><sZ>31 aut.</sZ></fA14><fA14 i1="03"><s1>Murdoch Childrens Research Institute</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>28 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Medical Genetics, University of Lausanne</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>6 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Pediatrics, Federico II University</s1><s2>80131 Naples</s2><s3>ITA</s3><sZ>7 aut.</sZ><sZ>23 aut.</sZ></fA14><fA14 i1="06"><s1>Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester</s1><s2>Manchester M13 9PT</s2><s3>GBR</s3><sZ>9 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="07"><s1>Departments of Molecular, Cell and Developmental Biology and Orthopaedic Surgery, University of California, Los Angeles (UCLA)</s1><s2>Los Angeles, CA 90048</s2><s3>USA</s3><sZ>11 aut.</sZ></fA14><fA14 i1="08"><s1>Ferguson Smith Centre for Clinical Genetics, Yorkhill Hospitals</s1><s2>Glasgow G3 8SJ</s2><s3>GBR</s3><sZ>12 aut.</sZ></fA14><fA14 i1="09"><s1>Radiology Department, Institute of Child Health, Great Ormond Street Hospital</s1><s2>London WC1N 3JH</s2><s3>GBR</s3><sZ>13 aut.</sZ></fA14><fA14 i1="10"><s1>Laboratory for Bone and Joint Diseases, Center for Genomic Medicine</s1><s2>Riken, Tokyo 108-8639</s2><s3>JPN</s3><sZ>14 aut.</sZ></fA14><fA14 i1="11"><s1>Clinical Genetics, Department of Genetics and Procreation, Centre Hospitalier Universitaire</s1><s2>38043 Grenoble</s2><s3>FRA</s3><sZ>15 aut.</sZ></fA14><fA14 i1="12"><s1>Institute of Human Genetics, Johann Wolfgang Goethe University Hospital</s1><s2>60590 Frankfurt/Main</s2><s3>DEU</s3><sZ>16 aut.</sZ></fA14><fA14 i1="13"><s1>Unité de Genetique médicale et Laboratoire associe Institut National de la Sante et de la Recherche Medicale, Universite Saint-Joseph, 11-5076 Riad El Solh</s1><s2>Beyrouth</s2><s3>LBN</s3><sZ>17 aut.</sZ></fA14><fA14 i1="14"><s1>Department of Radiology and Medical Imaging, Tokyo Metropolitan Children's Medical Center</s1><s2>Fuchu, Tokyo 183-8561</s2><s3>JPN</s3><sZ>18 aut.</sZ></fA14><fA14 i1="15"><s1>Medical Genetics Institute, Cedars-Sinai Medical Center</s1><s2>Los Angeles, CA 90048</s2><s3>USA</s3><sZ>19 aut.</sZ><sZ>21 aut.</sZ></fA14><fA14 i1="16"><s1>Department of Medical Genetics, University Hospital of Antwerp, University of Antwerp</s1><s2>2650 Edegem</s2><s3>BEL</s3><sZ>20 aut.</sZ></fA14><fA14 i1="17"><s1>Departments of Human Genetics, Pediatrics and Medicine, David Geffen School of Medicine at UCLA</s1><s2>Los Angeles, CA 90095-7088</s2><s3>USA</s3><sZ>21 aut.</sZ></fA14><fA14 i1="18"><s1>Greenwood Genetic Center</s1><s2>Greenville, SC 29605</s2><s3>USA</s3><sZ>22 aut.</sZ></fA14><fA14 i1="19"><s1>Department of Pediatrics, Miyazaki Medical College, University of Miyazaki, 5200 Kihara</s1><s2>Miyazaki 889-1692</s2><s3>JPN</s3><sZ>24 aut.</sZ></fA14><fA14 i1="20"><s1>Clinical Genetics, Great Ormond Street Hospital</s1><s2>London WC1N 3JH</s2><s3>GBR</s3><sZ>25 aut.</sZ></fA14><fA14 i1="21"><s1>Department of Medical Genetics, Centre Hospitalier Universitaire Vaudois</s1><s2>1011 Lausanne</s2><s3>CHE</s3><sZ>26 aut.</sZ></fA14><fA14 i1="22"><s1>Laboratory and Clinic for Inborn Errors Of Metabolism, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte</s1><s2>Minas Gerais 30130100</s2><s3>BRA</s3><sZ>27 aut.</sZ></fA14><fA14 i1="23"><s1>Department of Biochemistry and Molecular Biology, University of Melbourne</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>28 aut.</sZ></fA14><fA20><s1>767-772</s1></fA20><fA21><s1>2011</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>2610</s2><s5>354000505975750080</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>34 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0043068</s0></fA47><fA60><s1>P</s1><s3>C</s3></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>American journal of human genetics</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>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.</s0></fC01><fC02 i1="01" i2="X"><s0>002A04</s0></fC02><fC02 i1="02" i2="X"><s0>002A07</s0></fC02><fC02 i1="03" i2="X"><s0>002B23A</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Dysplasie</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Dysplasia</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Displasia</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Récidive</s0><s5>09</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Relapse</s0><s5>09</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Recaida</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Récidivant</s0><s5>10</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Recurrent</s0><s5>10</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Recidivante</s0><s5>10</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Caractère dominant</s0><s5>11</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Dominant character</s0><s5>11</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Carácter dominante</s0><s5>11</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Mutation</s0><s5>12</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Mutation</s0><s5>12</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Mutación</s0><s5>12</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Kinésine</s0><s5>13</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Kinesin</s0><s5>13</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Kinesina</s0><s5>13</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Os</s0><s5>14</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Bone</s0><s5>14</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Hueso</s0><s5>14</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Squelette</s0><s5>15</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Skeleton</s0><s5>15</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Esqueleto</s0><s5>15</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Articulation</s0><s5>16</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Joint</s0><s5>16</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Articulación</s0><s5>16</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Hyperlaxité</s0><s5>17</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Laxity</s0><s5>17</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Hiperlaxitud</s0><s5>17</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Génétique</s0><s5>18</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Genetics</s0><s5>18</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Genética</s0><s5>18</s5></fC03><fC03 i1="12" i2="X" l="FRE"><s0>Homme</s0><s5>19</s5></fC03><fC03 i1="12" i2="X" l="ENG"><s0>Human</s0><s5>19</s5></fC03><fC03 i1="12" i2="X" l="SPA"><s0>Hombre</s0><s5>19</s5></fC03><fN21><s1>023</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard><server><NO>PASCAL 12-0043068 INIST</NO><ET>Recurrent Dominant Mutations Affecting Two Adjacent Residues in the Motor Domain of the Monomeric Kinesin KIF22 Result in Skeletal Dysplasia and Joint Laxity</ET><AU>BOYDEN (Eric D.); CAMPOS-XAVIER (A. Belinda); KALAMAJSKI (Sebastian); CAMERON (Trevor L.); SUAREZ (Philippe); TANACKOVICH (Goranka); ANDRIA (Generoso); BALLHAUSEN (Diana); BRIGGS (Michael D.); HARTLEY (Claire); COHN (Daniel H.); ROSEMARIE DAVIDSON (H.); HALL (Christine); IKEGAWA (Shiro); JOUK (Pierre-Simon); KÖNIG (Rainer); MEGARBANE (Andre); NISHIMURA (Gen); LACHMAN (Ralph S.); MORTIER (Geert); RIMOIN (David L.); CURTIS ROGERS (R.); ROSSI (Massimiliano); SAWADA (Hirotake); SCOTT (Richard); UNGER (Sheila); RIBEIRO VALADARES (Eugenia); BATEMAN (John F.); WARMAN (Matthew L.); SUPERTI-FURGA (Andrea); BONAFE (Luisa)</AU><AF>Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School/Boston, MA 02115/Etats-Unis (1 aut., 3 aut., 29 aut.); Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois/1011 Lausanne/Suisse (2 aut., 5 aut., 8 aut., 30 aut., 31 aut.); Murdoch Childrens Research Institute/Parkville, Victoria 3052/Australie (4 aut., 28 aut.); Department of Medical Genetics, University of Lausanne/1011 Lausanne/Suisse (6 aut.); Department of Pediatrics, Federico II University/80131 Naples/Italie (7 aut., 23 aut.); Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester/Manchester M13 9PT/Royaume-Uni (9 aut., 10 aut.); Departments of Molecular, Cell and Developmental Biology and Orthopaedic Surgery, University of California, Los Angeles (UCLA)/Los Angeles, CA 90048/Etats-Unis (11 aut.); Ferguson Smith Centre for Clinical Genetics, Yorkhill Hospitals/Glasgow G3 8SJ/Royaume-Uni (12 aut.); Radiology Department, Institute of Child Health, Great Ormond Street Hospital/London WC1N 3JH/Royaume-Uni (13 aut.); Laboratory for Bone and Joint Diseases, Center for Genomic Medicine/Riken, Tokyo 108-8639/Japon (14 aut.); Clinical Genetics, Department of Genetics and Procreation, Centre Hospitalier Universitaire/38043 Grenoble/France (15 aut.); Institute of Human Genetics, Johann Wolfgang Goethe University Hospital/60590 Frankfurt/Main/Allemagne (16 aut.); Unité de Genetique médicale et Laboratoire associe Institut National de la Sante et de la Recherche Medicale, Universite Saint-Joseph, 11-5076 Riad El Solh/Beyrouth/Liban (17 aut.); Department of Radiology and Medical Imaging, Tokyo Metropolitan Children's Medical Center/Fuchu, Tokyo 183-8561/Japon (18 aut.); Medical Genetics Institute, Cedars-Sinai Medical Center/Los Angeles, CA 90048/Etats-Unis (19 aut., 21 aut.); Department of Medical Genetics, University Hospital of Antwerp, University of Antwerp/2650 Edegem/Belgique (20 aut.); Departments of Human Genetics, Pediatrics and Medicine, David Geffen School of Medicine at UCLA/Los Angeles, CA 90095-7088/Etats-Unis (21 aut.); Greenwood Genetic Center/Greenville, SC 29605/Etats-Unis (22 aut.); Department of Pediatrics, Miyazaki Medical College, University of Miyazaki, 5200 Kihara/Miyazaki 889-1692/Japon (24 aut.); Clinical Genetics, Great Ormond Street Hospital/London WC1N 3JH/Royaume-Uni (25 aut.); Department of Medical Genetics, Centre Hospitalier Universitaire Vaudois/1011 Lausanne/Suisse (26 aut.); Laboratory and Clinic for Inborn Errors Of Metabolism, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte/Minas Gerais 30130100/Brésil (27 aut.); Department of Biochemistry and Molecular Biology, University of Melbourne/Parkville, Victoria 3052/Australie (28 aut.)</AF><DT>Publication en série; Compte-rendu; Niveau analytique</DT><SO>American journal of human genetics; ISSN 0002-9297; Coden AJHGAG; Etats-Unis; Da. 2011; Vol. 89; No. 6; Pp. 767-772; Bibl. 34 ref.</SO><LA>Anglais</LA><EA>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.</EA><CC>002A04; 002A07; 002B23A</CC><FD>Dysplasie; Récidive; Récidivant; Caractère dominant; Mutation; Kinésine; Os; Squelette; Articulation; Hyperlaxité; Génétique; Homme</FD><ED>Dysplasia; Relapse; Recurrent; Dominant character; Mutation; Kinesin; Bone; Skeleton; Joint; Laxity; Genetics; Human</ED><SD>Displasia; Recaida; Recidivante; Carácter dominante; Mutación; Kinesina; Hueso; Esqueleto; Articulación; Hiperlaxitud; Genética; Hombre</SD><LO>INIST-2610.354000505975750080</LO><ID>12-0043068</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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