Figure 4.

Mesoscopic hypotheses underlying the pathophysiology of CASK-related disorders as well as other X-linked neurological disorders in female patients. (A) All the somatic cells in male patients express a pathogenic mutant of the CASK protein (the rightmost), except for somatic mosaic cases of males. Female patients consist of a mixture of CASK-expressing (white) and -deficient (red) cells and the proportion of the two genotypes of cells may determine the severity of CASK-related disorders. (B) CASK-deficient neurons (red) are connected more preferentially to each other, and synaptic connections between CASK-expressing neurons are weaker. The “neurocircuit interference”, a genotype-independent neural circuitry, may explain the pathogenesis of CASK-related disorders.