| 1. |
- Buxbaum, Joseph. D., et al.
(author)
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Mutation analysis of the NSD1 gene in patients with autism spectrum disorders and macrocephaly.
- 2007
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In: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 8
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Journal article (peer-reviewed)abstract
- ABSTRACT: BACKGROUND: Sotos syndrome is an overgrowth syndrome characterized by macrocephaly, advanced bone age, characteristic facial features, and learning disabilities, caused by mutations or deletions of the NSD1 gene, located at 5q35. Sotos syndrome has been described in a number of patients with autism spectrum disorders, suggesting that NSD1 could be involved in other cases of autism and macrocephaly. METHODS: We screened the NSD1 gene for mutations and deletions in 88 patients with autism spectrum disorders and macrocephaly (head circumference 2 standard deviations or more above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions. Dosage analysis of NSD1 was carried out using multiplex ligation-dependent probe amplification. RESULTS: We identified three missense variants (R604L, S822C and E1499G) in one patient each, but none is within a functional domain. In addition, segregation analysis showed that all variants were inherited from healthy parents and in two cases were also present in unaffected siblings, indicating that they are probably nonpathogenic. No partial or whole gene deletions/duplications were observed. CONCLUSIONS: Our findings suggest that Sotos syndrome is a rare cause of autism spectrum disorders and that screening for NSD1 mutations and deletions in patients with autism and macrocephaly is not warranted in the absence of other features of Sotos syndrome.
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| 2. |
- Buxbaum, Joseph D, et al.
(author)
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Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.
- 2007
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In: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 144B:4, s. 484-491
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Journal article (peer-reviewed)abstract
- Mutations in the PTEN gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease. In addition, PTEN mutations have been described in a few patients with autism spectrum disorders (ASDs) and macrocephaly. In this study, we screened the PTEN gene for mutations and deletions in 88 patients with ASDs and macrocephaly (defined as >or=2 SD above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions, as well as the promoter region. Dosage analysis of PTEN was carried out using multiplex ligation-dependent probe amplification (MLPA). No partial or whole gene deletions were observed. We identified a de novo missense mutation (D326N) in a highly conserved amino acid in a 5-year-old boy with autism, mental retardation, language delay, extreme macrocephaly (+9.6 SD) and polydactyly of both feet. Polydactyly has previously been described in two patients with Lhermitte-Duclos disease and CS and is thus likely to be a rare sign of PTEN mutations. Our findings suggest that PTEN mutations are a relatively infrequent cause of ASDs with macrocephaly. Screening of PTEN mutations is warranted in patients with autism and pronounced macrocephaly, even in the absence of other features of PTEN-related tumor syndromes.
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| 3. |
- Chaste, Pauline, et al.
(author)
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Mutation screening of the ARX gene in patients with autism.
- 2007
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In: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 144B:2, s. 228-230
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Journal article (peer-reviewed)abstract
- Mutations in the Aristaless related homeobox (ARX) gene are associated with a broad spectrum of disorders, including nonsyndromic X-linked mental retardation, sometimes associated with epilepsy, as well as syndromic forms with brain abnormalities and abnormal genitalia. Furthermore, ARX mutations have been described in a few patients with autism or autistic features. In this study, we screened the ARX gene in 226 male patients with autism spectrum disorders and mental retardation; 42 of the patients had epilepsy. The mutation analysis was performed by direct sequencing of all exons and flanking regions. No ARX mutations were identified in any of the patients tested. These findings indicate that mutations in the ARX gene are very rare in autism.
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| 4. |
- Durand, Christelle. M., et al.
(author)
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Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.
- 2007
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:1, s. 25-27
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Journal article (peer-reviewed)abstract
- SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders.
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| 5. |
- Szatmari, Peter, et al.
(author)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Journal article (peer-reviewed)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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