Developmental and cytological phenotypes of cohesinopathies and potentially related maladies.

<p>Partial list of developmental and cytological effects in response to cohesion pathway mutations.</p>*<p>Craniofacial dysmorphia include micrognathia, ear abnormalities, wide-set eyes, beaked or prominent nose, arched eyebrows, or low-set ears.</p>+<p>Limb reductions are often symmetric and involve all four limbs in RBS but predominant in upper extremities in CdLS. Limb reduction appears limited to the radius in NBS and FA.</p>**<p>Organ abnormalities may include renal, urinary, gonadal, gastroesophageal, and others.</p>++<p>Detection of cryptic HR/PCS may require cell exposure to mitomycin. ND (Not Diagnostic): most studies document that HR/PCS is not elevated in CdLS cells <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Revenkova1" target="_blank">[17]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Castronovo1" target="_blank">[18]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Vrouwe1" target="_blank">[20]</a>, but see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Kaur1" target="_blank">[48]</a>. While HR/PCS is thus not efficacious as a diagnostic tool, numerous chromosomal aberrations are evident in CdLS cells upon exposure to genotoxic agents <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Vrouwe1" target="_blank">[20]</a>, revealing that CdLS cells may be predispositioned to PCS/HR. Bolded text represents examples of historical cytological diagnostic markers (HR/PCS for RBS, Clastogen sensitivity for FA). Phenotypes shown for potentially cohesinopathic-related developmental maladies (Ribosomopathies TCS and DBA, Nijmegen Breakage Disease, Fanconi Anemia—last four columns) that we speculate are similarly predicated on transcriptional dysregulation <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Vega1" target="_blank">[1]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Schule1" target="_blank">[2]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Musio1" target="_blank">[5]</a>–<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Krantz1" target="_blank">[8]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Morita1" target="_blank">[14]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Liu1" target="_blank">[26]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Gimigliano1" target="_blank">[33]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Leem1" target="_blank">[41]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Kaur1" target="_blank">[48]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-vanderLelij1" target="_blank">[55]</a>–<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-CapoChichi1" target="_blank">[57]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-vanderLelij3" target="_blank">[61]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Kee1" target="_blank">[63]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Auerbach1" target="_blank">[78]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004036#pgen.1004036-Genetics1" target="_blank">[79]</a>.</p