RT Journal Article SR Electronic T1 Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin–Siris syndrome JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 152 OP 162 DO 10.1136/jmedgenet-2015-103393 VO 53 IS 3 A1 Annmarie Hempel A1 Alistair T Pagnamenta A1 Moira Blyth A1 Sahar Mansour A1 Vivienne McConnell A1 Ikuyo Kou A1 Shiro Ikegawa A1 Yoshinori Tsurusaki A1 Naomichi Matsumoto A1 Adriana Lo-Castro A1 Ghislaine Plessis A1 Beate Albrecht A1 Agatino Battaglia A1 Jenny C Taylor A1 Malcolm F Howard A1 David Keays A1 Aman Singh Sohal A1 DDD collaboration A1 Susanne J Kühl A1 Usha Kini A1 Alisdair McNeill YR 2016 UL http://jmg.bmj.com/content/53/3/152.abstract AB Background SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin–Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders.Methods We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression.Results We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin–Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly.Conclusions We thus propose that SOX11 deletion or mutation can present with a Coffin–Siris phenotype.