De Novo SYNGAP1 Mutations in Nonsyndromic Intellectual Disability and Autism

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• 作者：Fadi F. Hamdan^a ; Hussein Daoud^b ; Am&#xe9 ; lie Piton^b ; Julie Gauthier^b ; Sylvia Dobrzeniecka^b ; Marie-Odile Krebs^g ; Ridha Joober^c ; Jean-Claude Lacaille^d ; Am&#xe9 ; lie Nadeau^a ; Jeff M. Milunsky^h ; Zhenyuan Wang^h ; Lionel Carmant^a ; Laurent Mottron^e ; Miriam H. Beauchamp^a ; ^f ; Guy A. Rouleau^a ; ^b ; Jacques L. Michaud^a ; ^{jacques.michaud@recherche-ste-justine.qc.ca}
• 关键词：Autism ; de novo mutation ; epilepsy ; intellectual disability ; mental retardation ; SYNGAP1
• 刊名：Biological Psychiatry
• 出版年：2011
• 出版时间：1 May 2011
• 年：2011
• 卷：69
• 期：9
• 页码：898-901
• 全文大小：354 K

文摘

Background

Little is known about the genetics of nonsyndromic intellectual disability (NSID). Recently, we reported de novo truncating mutations in the SYNGAP1 gene of 3 of 94 NSID cases, suggesting that its disruption represents a common cause of autosomal dominant NSID.

Methods

To further explore the involvement of SYNGAP1 in NSID, we sequenced its exons and intronic boundaries in 60 additional sporadic cases of NSID, including 30 patients with autism spectrum disorders (ASD) and 9 with epilepsy, and in 380 control individuals.

Results

We identified de novo out-of-frame deletions in two patients with NSID and mild generalized epilepsy (c.2677delC/p.Q893RfsX184 and c.321_324delGAAG/p. K108VfsX25) and a de novo splicing mutation (c.2294 + 1G>A), which results in the creation of a premature stop codon, in a patient with NSID and autism. No splicing or truncating mutations were found in control subjects.

Conclusions

We provide evidence that truncating mutations in SYNGAP1 are common in NSID and can be also associated with autism.