A de novo X;8 translocation creates a PTK2-THOC2 gene fusion with THOC2 expression knockdown in a patient with psychomotor retardation and congenital cerebellar hypoplasia

Non-progressive cerebellar hypoplasias are rare developmental disorders leading to movement incoordination and intellectual disability. In an affected eight year-old girl, we identified an exchange between chromosomes X and 8 (translocation X;8). The Protein Tyrosine Kinase 2 (PTK2) and THO complex 2 (THOC2) gene structure was altered and both proteins were reduced to at least half dose. We studied THOC2 reduction in cellular and an animal model (C. elegans), and propose that it can play key roles in neuron development, and possibly in combination with PTK2 decrease, may affect normal neural network formation, leading to cognitive impairment and cerebellar congenital hypoplasia. (By Dr. Alfredo Brusco, http://jmg.bmj.com/content/early/2013/06/06/jmedgenet-2013-101542 )