{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:24:26Z","timestamp":1789914266389,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,10,14]],"date-time":"2017-10-14T00:00:00Z","timestamp":1507939200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission, Pakistan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Autosomal recessive primary microcephaly (MCPH) is a rare condition characterized by a reduced cerebral cortex accompanied with intellectual disability. Mutations in 17 genes have been shown to cause this phenotype. Recently, mutations in\n                      <jats:italic>CIT,<\/jats:italic>\n                      encoding CRIK (citron rho\u2010interacting kinase)\u2014a component of the central spindle matrix\u2014were added. We aimed at identifying novel MCPH\u2010associated genes and exploring their functional role in pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Linkage analysis and whole exome sequencing were performed in consanguineous and nonconsanguineous MCPH families to identify disease\u2010causing variants. Functional consequences were investigated by RNA studies and on the cellular level using immunofluorescence and microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified homozygous mutations in\n                      <jats:italic>KIF14<\/jats:italic>\n                      (NM_014875.2;c.263T&gt;A;pLeu88*, c.2480_2482delTTG; p.Val827del, and c.4071G&gt;A;p.Gln1357=) as the likely cause in 3 MCPH families. Furthermore, in a patient presenting with a severe form of primary microcephaly and short stature, we identified compound heterozygous missense mutations in\n                      <jats:italic>KIF14<\/jats:italic>\n                      (NM_014875.2;c.2545C&gt;G;p.His849Asp and c.3662G&gt;T;p.Gly1221Val). Three of the 5 identified mutations impaired splicing, and 2 resulted in a truncated protein. Intriguingly,\n                      <jats:italic>Kif14<\/jats:italic>\n                      knockout mice also showed primary microcephaly. Human kinesin\u2010like protein KIF14, a microtubule motor protein, localizes at the midbody to finalize cytokinesis by interacting with CRIK. We found impaired localization of both KIF14 and CRIK at the midbody in patient\u2010derived fibroblasts. Furthermore, we observed a large number of binucleated and apoptotic cells\u2014signs of failed cytokinesis that we also observed in experimentally KIF14\u2010depleted cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Our data corroborate the role of an impaired cytokinesis in the etiology of primary and syndromic microcephaly, as has been proposed by recent findings on\n                      <jats:italic>CIT<\/jats:italic>\n                      mutations. Ann Neurol 2017;82:562\u2013577\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25044","type":"journal-article","created":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T12:22:45Z","timestamp":1505132565000},"page":"562-577","source":"Crossref","is-referenced-by-count":85,"title":["Mutations of\n                    <i>KIF14<\/i>\n                    cause primary microcephaly by impairing cytokinesis"],"prefix":"10.1002","volume":"82","author":[{"given":"Abubakar","family":"Moawia","sequence":"first","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"},{"name":"Institute of Biochemistry I, Medical Faculty University of Cologne Cologne Germany"},{"name":"Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering Pakistan Institute of Engineering and Applied Sciences Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranad","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajida","family":"Rasool","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"},{"name":"Institute of Biochemistry and Biotechnology, Quaid\u2010e\u2010Azam Campus University of the Punjab Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syeda Seema","family":"Waseem","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"},{"name":"Institute of Biochemistry I, Medical Faculty University of Cologne Cologne Germany"},{"name":"Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering Pakistan Institute of Engineering and Applied Sciences Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Ewida","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Budde","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Kawalia","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Motameny","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal","family":"Khan","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering Pakistan Institute of Engineering and Applied Sciences Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambrin","family":"Fatima","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering Pakistan Institute of Engineering and Applied Sciences Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Jameel","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering Pakistan Institute of Engineering and 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Anna","family":"Noegel","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"},{"name":"Institute of Biochemistry I, Medical Faculty University of Cologne Cologne Germany"},{"name":"Center for Molecular Medicine Cologne University of Cologne Cologne Germany"},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging\u2010Associated Diseases University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Al\u2010Owain","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics King Faisal Specialist Hospital Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstanze","family":"H\u00f6rtnagel","sequence":"additional","affiliation":[{"name":"Center for Genomics and Transcriptomics T\u00fcbingen 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