Figure 6. Schematic illustration of the cellular interference mechanism associated with PCDH19 mutations.

A) In normal individuals, characterized by a homogeneous population of PCDH19-positive cells, neurons are able to form normal neuronal networks; B) In mutated male patients, hemizygosity leads to a homogeneous population of PCDH19-negative cells; in this condition, neurons preserve the ability to form normal neuronal networks; C) In heterozygous mutated females, random X inactivation leads to the co-existence of two PCDH19-positive and PCDH19-negative cell populations. These two cell populations cause divergent cell sorting and migration (due to attractive or repulsive interactions) and lead to abnormal neuronal networks. Somatic mosaicism in mutated males gives rise to the same pathological situation. The precise mechanisms by which the neuronal networks are altered are still unknown.