Figure 3.

CNTNAP2 heterozygous missense variants could induce a continuum of phenotypes when Caspr2 functions are dose-dependent. (A) Variant proteins display a gradient of intracellular retention in transfected COS-7 cells. Percentage of intracellular form for each variant protein normalized to its total expression, evaluated by immunoblot. Data are means ± SEM of 3 independent experiments (see original manuscript). (B) The phenotypic consequences of each variant could result from the combination of a dominant-negative effect on wild-type Caspr2 function through retention in the endoplasmic reticulum (ER) and a loss of function at the plasma membrane (adhesion defects) because of structural changes, leading to variable level of functional protein at the plasma membrane, and as a whole to a continuum of phenotypes.