Symptomatic epilepsy and skull dysplasia due to a homozygous <i>SNIP1</i> mutation.

<p>(<b>A</b>) Two affected brothers presented with severe psychomotor delay, intractable seizures, bulbous nose, wide mouth and tongue, broad jaw with protuberant angles, short hands, short tapered fingers, and broad thumbs. (<b>B,C</b>) Brain MRI (B, axial T2; C, coronal T1) MRI showed enlarged ventricles, a thin corpus callosum, hypomyelination, and an irregular, undulating skull surface. (<b>D</b>) Mouse FLAG-SNIP1 (wt) fusion protein, when transiently overexpressed in mIMCD3 cells, localizes to the nucleus in a punctate pattern consistent with transcriptional complexes. (<b>E</b>) Mouse FLAG-SNIP1 (p.Glu353Gly) localizes to the nucleus, but with a more aggregated distribution. (<b>F</b>) <i>Top</i> – Reverse-transcriptase PCR from three wild-type mSNIP1-transfected samples and four c.1058A>G mSNIP1-transfected samples. mSNIP1 amplicon – 400 bp. mGAPDH (loading control) – 1037 bp amplicon. <i>Bottom</i> – Western blot of lysates from mIMCD3 cells transiently transfected with wt (lanes wt_1&2) or c.1058A>G (lanes p.Glu353Gly_1&2) mSNIP1 displaying the FLAG-mSNIP fusion protein at ∼48 kDa. The 140-kDa non-specific band was used as a loading control. Data shown are two out of four replicate sets of transfections.