PURPOSE: De novo STXBP1 mutations have been found in individuals with early 
infantile epileptic encephalopathy with suppression-burst pattern (EIEE). Our 
aim was to delineate the clinical spectrum of subjects with STXBP1 mutations, 
and to examine their biologic aspects.
METHODS: STXBP1 was analyzed in 29 and 54 cases of cryptogenic EIEE and West 
syndrome, respectively, as a second cohort. RNA splicing was analyzed in 
lymphoblastoid cells from a subject harboring a c.663 + 5G>A mutation. 
Expression of STXBP1 protein with missense mutations was examined in 
neuroblastoma2A cells.
RESULTS: A total of seven novel STXBP1 mutations were found in nine EIEE cases, 
but not in West syndrome. The mutations include two frameshift mutations, three 
nonsense mutations, a splicing mutation, and a recurrent missense mutation in 
three unrelated cases. Including our previous data, 10 of 14 individuals (71%) 
with STXBP1 aberrations had the onset of spasms after 1 month, suggesting 
relatively later onset of epileptic spasms. Nonsense-mediated mRNA decay 
associated with abnormal splicing was demonstrated. Transient expression 
revealed that STXBP1 proteins with missense mutations resulted in degradation in 
neuroblastoma2A cells.
DISCUSSION: Collectively, STXBP1 aberrations can account for about one-third 
individuals with EIEE (14 of 43). These genetic and biologic data clearly showed 
that haploinsufficiency of STXBP1 is the important cause for cryptogenic EIEE.