New Bone Dysplasia with Cloudy Cornea and Intellectual Disability caused by homozygous PLCB3 variants

Ben-Salem, Robbins et al. reports a new form of syndromic bone dysplasia in two Emirati first cousins. This new syndrome includes profound limb shortening with spine and pelvis abnormalities, corneal clouding, and intellectual disability. Homozygosity mapping in the family localized the genetic cause to cytogenetic band 11q12.1-q13.1. Whole exome sequencing identified a homozygous variant, c.2632G>T,  in PLCB3 as a strong candidate gene. The group confirmed the pathogenicity of this variant both by protein modelling and in transfected cells and patient fibroblasts, which both show disordered cytoskeletal organization and highly elevated levels of the lipid, PIP2, that is broken down by PLCB3. (By Sarah M. Robbins and Salma Ben-Salem, http://jmg.bmj.com/content/early/2017/11/09/jmedgenet-2017-104827 )