对与异常皮层发育相关的基因位点的识别，因遗传异质性、小家庭规模和不能反映分子发病机制的诊断分类而复杂化。
这些障碍在一项采用“全外显子组”(whole-exome)测序方法的研究中已被克服。在“WD重复区域-62” (WDR62)基因上所发生的隐性突变，被发现引起一系列看起来迥然不同的脑异常，包括小头症、巨脑回和小脑发育不良（在一例中发现有这种异常）。
与其他已知的小头症基因不同的是，WDR62不与中心体结合；它从位置上来讲主要在细胞核中，并且在胚胎神经发生过程中在新皮层中瞬时表达。（生物谷Bioon.com）
生物谷推荐英文摘要：
Nature doi:10.1038/nature09327
Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations
Kaya Bilgüvar,Ali Kemal ?ztürk,Angeliki Louvi,Kenneth Y. Kwan,Murim Choi,Burak Tatl?,Dilek Yaln?zo?lu,Beyhan Tüysüz,Ahmet Okay ?a?layan,Sarenur G?kben,Hande Kaymak?alan,Tanyeri Barak,Mehmet Bak?rc?o?lu,Katsuhito Yasuno,Winson Ho,Stephan Sanders,Ying Zhu,Sanem Y?lmaz,Alp Din?er,Michele H. Johnson,Richard A. Bronen,Naci Ko?er,Hüseyin Per,Shrikant Mane,Mehmet Necmettin Pamir,Cengiz Yal??nkaya,Sefer Kumanda?,Meral Top?u,Meral ?zmen,Nenad ?estan,Richard P. Lifton,richard.lifton@yale.eduMatthew W. Statematthew.state@yale.edu& Murat Günel
The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers1, 2. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development3, 4, 5, 6. Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with mutations in WDR62 had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. Expression of WDR62 in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.
