Figure 1.

Pathogenic STXBP1 mutations. (a) Positions of the reported pathogenic STXBP1 mutations. Missense mutations reported to cause Ohatahra syndrome⁶ are indicated on top of the STXBP1 sequence, while splicing and truncating mutations reported in NSID with nonspecific epilepsy⁷ (c.169+1G>A and p.R388X) or without epilepsy (current study, p.Y402X, highlighted) are shown below the STXBP1 sequence. The positions of the various STXBP1 protein domains are depicted based on the rat STXBP1 crystal structure.⁸ (b) Chromatograms of the STXBP1 de novo mutation identified in patient 3 and the corresponding representative sequence from parents of patient 3 (both the mother's and father's STXBP1 sequences lack c.1206delT mutation). Wild-type (WT) and mutant (MT) STXBP1 DNA sequences are shown along with their corresponding amino acids. Numbering of the coding nucleotides and amino acids are based on isoform a of STXBP1 (Refseq NM_003165).