Sporadic Infantile Epileptic Encephalopathy Caused by Mutations in PCDH19 Resembles Dravet Syndrome but Mainly Affects Females (original) (raw)
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.