{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T06:32:33Z","timestamp":1792305153057,"version":"4.4.0"},"reference-count":131,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,5,9]],"date-time":"2014-05-09T00:00:00Z","timestamp":1399593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>The underlying etiologies of genetic congenital microcephaly are complex and multifactorial. Recently, with the exponential growth in the identification and characterization of novel genetic causes of congenital microcephaly, there has been a consolidation and emergence of certain themes concerning underlying pathomechanisms. These include abnormal mitotic microtubule spindle structure, numerical and structural abnormalities of the centrosome, altered cilia function, impaired DNA repair, DNA Damage Response signaling and DNA replication, along with attenuated cell cycle checkpoint proficiency. Many of these processes are highly interconnected. Interestingly, a defect in a gene whose encoded protein has a canonical function in one of these processes can often have multiple impacts at the cellular level involving several of these pathways. Here, we overview the key pathomechanistic themes underlying profound congenital microcephaly, and emphasize their interconnected nature. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.c.31397","type":"journal-article","created":{"date-parts":[[2014,5,9]],"date-time":"2014-05-09T17:35:35Z","timestamp":1399656935000},"page":"124-139","source":"Crossref","is-referenced-by-count":128,"title":["Congenital microcephaly"],"prefix":"10.1002","volume":"166","author":[{"given":"Diana","family":"Alcantara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"O'Driscoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.01.027"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970627)70:4<454::AID-AJMG23>3.0.CO;2-F"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1155"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1674"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2180"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.775"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.776"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2008.10.015"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng995"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2005.00508.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.16830211"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","unstructured":"BuckD MalivertL de ChassevalR BarraudA FondanecheM\u2010C SanalO PlebaniA StephanJ\u2010L HufnagelM le DeistF FischerA DurandyA de VillartayJ\u2010P RevyP.2006. Cernunnos a novel nonhomologous end\u2010joining factor is mutated in human immunodeficiency with microcephaly. Cell124:287\u2013299.","DOI":"10.1016\/j.cell.2005.12.030"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(02)00833-X"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2380"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22226"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81175-7"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-100803"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2450"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201007107"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010biochem\u2010060713\u2010035428"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2097"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-01-00201.2001"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-110711-155540"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0421"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604066103"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1324-11.2011"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.090501.150203"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds386"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.89"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61014"},{"key":"e_1_2_8_32_1","first-page":"39","article-title":"Malformation syndromes. A selected miscellany","volume":"11","author":"Gorlin R","year":"1975","journal-title":"Birth Defects Orig Artic Ser"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.80"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2342"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.777"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2009.12.002"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1449"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.4.1283"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1166745"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5366.1089"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-051710-150955"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1012"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.894001"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60224"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-59"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2009.10.003"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1086\/302640"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.3109\/10409230903578593"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58321"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2013.04.016"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.195248.112"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00815-10"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.09.005"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600375"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.12.041"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10956"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12517"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2514"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e3283444d05"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3097"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.493"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2248"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.893"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2224"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-39"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012716"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2010.12.002"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1140321"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1086\/303022"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.569"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2009.04.017"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010014\u20101443\u20103"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-124420"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00427-006-0065-8"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-102108-134222"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01093.x"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00309-9"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2851"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026496"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.420"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22461"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2011.0072"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601396"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.130065"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2009.09.001"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00408-7"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1746"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2008.03.018"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1129"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012773"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002945"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602436103"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909894106"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2613"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl022"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002310"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)93934-P"},{"key":"e_1_2_8_98_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1151174"},{"key":"e_1_2_8_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.10.029"},{"key":"e_1_2_8_100_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12370"},{"key":"e_1_2_8_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.07.007"},{"key":"e_1_2_8_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(96)80077-9"},{"key":"e_1_2_8_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.09.012"},{"key":"e_1_2_8_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2013.06.005"},{"key":"e_1_2_8_105_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.160572.113"},{"key":"e_1_2_8_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.05.025"},{"key":"e_1_2_8_107_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100585"},{"key":"e_1_2_8_108_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.526"},{"key":"e_1_2_8_109_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3546"},{"key":"e_1_2_8_110_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.971"},{"key":"e_1_2_8_111_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012724"},{"key":"e_1_2_8_112_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-3471-7_7"},{"key":"e_1_2_8_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.04.028"},{"key":"e_1_2_8_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.02.026"},{"key":"e_1_2_8_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81547-0"},{"key":"e_1_2_8_116_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003360"},{"key":"e_1_2_8_117_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707579104"},{"key":"e_1_2_8_118_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-110410-132435"},{"key":"e_1_2_8_119_1","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.88"},{"key":"e_1_2_8_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2009.09.011"},{"key":"e_1_2_8_121_1","first-page":"91","article-title":"A DNA\u2010PKcs mutation in a radiosensitive T\u2013B\u2013 SCID patient inhibits Artemis activation and nonhomologous end\u2010joining","volume":"119","author":"van der Burg M","year":"2009","journal-title":"J Clin Invest"},{"key":"e_1_2_8_122_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.008"},{"key":"e_1_2_8_123_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81174-5"},{"key":"e_1_2_8_124_1","volume-title":"GeneReviews[R]","author":"Verloes A","year":"2013"},{"key":"e_1_2_8_125_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2832"},{"key":"e_1_2_8_126_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.04.010"},{"key":"e_1_2_8_127_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2670"},{"key":"e_1_2_8_128_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2011.01.006"},{"key":"e_1_2_8_129_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67349"},{"key":"e_1_2_8_130_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2012-302882"},{"key":"e_1_2_8_131_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-7687-6_2"},{"key":"e_1_2_8_132_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-11-0796"}],"container-title":["American Journal of Medical Genetics Part C: Seminars in Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.c.31397","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.31397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T12:44:17Z","timestamp":1694609057000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.c.31397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,9]]},"references-count":131,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["10.1002\/ajmg.c.31397"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.c.31397","archive":["Portico"],"relation":{},"ISSN":["1552-4868","1552-4876"],"issn-type":[{"value":"1552-4868","type":"print"},{"value":"1552-4876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,9]]}}}