De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy
Annals of Neurology: Official Journal of the American Neurological …, 2009•Wiley Online Library
We sequenced genes coding for components of the SNARE complex (STX1A, VAMP2,
SNAP25) and their regulatory proteins (STXBP1/Munc18‐1, SYT1), which are essential for
neurotransmission, in 95 patients with idiopathic mental retardation. We identified de novo
mutations in STXBP1 (nonsense, p. R388X; splicing, c. 169+ 1G> A) in two patients with
severe mental retardation and nonsyndromic epilepsy. Reverse transcriptase polymerase
chain reaction and sequencing showed that the splicing mutation creates a stop codon …
SNAP25) and their regulatory proteins (STXBP1/Munc18‐1, SYT1), which are essential for
neurotransmission, in 95 patients with idiopathic mental retardation. We identified de novo
mutations in STXBP1 (nonsense, p. R388X; splicing, c. 169+ 1G> A) in two patients with
severe mental retardation and nonsyndromic epilepsy. Reverse transcriptase polymerase
chain reaction and sequencing showed that the splicing mutation creates a stop codon …
Abstract
We sequenced genes coding for components of the SNARE complex (STX1A, VAMP2, SNAP25) and their regulatory proteins (STXBP1/Munc18‐1, SYT1), which are essential for neurotransmission, in 95 patients with idiopathic mental retardation. We identified de novo mutations in STXBP1 (nonsense, p.R388X; splicing, c.169+1G>A) in two patients with severe mental retardation and nonsyndromic epilepsy. Reverse transcriptase polymerase chain reaction and sequencing showed that the splicing mutation creates a stop codon downstream of exon‐3. No de novo or deleterious mutations in STXBP1 were found in 190 control subjects, or in 142 autistic patients. These results suggest that STXBP1 disruption is associated with autosomal dominant mental retardation and nonsyndromic epilepsy. Ann Neurol 2009;65:748–753
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