De Novo STXBP1 Mutations in Mental Retardation and Nonsyndromic Epilepsy

被引：125

作者：

Hamdan, Fadi F. ^{[1
,2
]}

Piton, Amelie ^{[3
,4
]}

Gauthier, Julie ^{[3
,4
]}

Lortie, Anne ^{[1
,2
]}

Dubeau, Francois ^{[5
]}

Dobrzeniecka, Sylvia ^{[3
,4
]}

Spiegelman, Dan ^{[3
,4
]}

Noreau, Anne ^{[3
,4
]}

Pellerin, Stephanie ^{[1
,2
]}

Cote, Melanie ^{[3
,4
]}

Henrion, Edouard ^{[3
,4
]}

Fombonne, Eric ^{[6
]}

Mottron, Laurent ^{[7
]}

Marineau, Claude ^{[3
,4
]}

Drapeau, Pierre ^{[8
]}

Lafreniere, Ronald G. ^{[3
,4
]}

Lacaille, Jean Claude ^{[9
]}

Rouleau, Guy A. ^{[3
,4
]}

Michaud, Jacques L. ^{[1
,2
]}

机构：

[1] CHU St Justine, Res Ctr, Synapse Dis Grp, Montreal, PQ H3T 1C5, Canada

[2] Univ Montreal, Ctr Excellence Neur, Montreal, PQ, Canada

[3] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada

[4] CHU Montreal, Res Ctr, Montreal, PQ, Canada

[5] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada

[6] McGill Univ, Montreal Childrens Hosp, Dept Psychiat, Montreal, PQ H3A 2B4, Canada

[7] Univ Montreal, Hop Riviere des Prairies, Ctr Rech Fernand Seguin, Montreal, PQ, Canada

[8] Univ Montreal, Dept Pathol & Cell Biol, Grp Rech Syst Nerveux Cent, Montreal, PQ, Canada

[9] Univ Montreal, Dept Physiol, Grp Rech Syst Nerveux Cent, Montreal, PQ H3C 3J7, Canada

来源：

ANNALS OF NEUROLOGY | 2009年 / 65卷 / 06期

关键词：

SYNAPTIC VESICLE FUSION; MEMBRANE-FUSION; SNARE COMPLEX; MUNC18-1; SYNTAXIN; ENCEPHALOPATHY; SECRETION; DOCKING;

D O I：

10.1002/ana.21625

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：748 / 753

页数：6

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