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Mutation analysis of the NSD1 gene in patients with autism spectrum disorders and macrocephaly

Buxbaum, Joseph D; Cai, Guiqing; Nygren, Gudrun; Chaste, Pauline; Delorme, Richard; Goldsmith, Juliet; Råstam, Maria LU ; Silverman, Jeremy M; Hollander, Eric and Gillberg, Christopher, et al. (2007) In BMC Medical Genetics 8(68).
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... (More)
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.



Conclusion:

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. (Less)
Please use this url to cite or link to this publication:
@article{8ba63934-ff51-4205-b06f-e7ac4df0c44e,
  abstract     = {Background:<br/><br>
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.<br/><br>
<br/><br>
Methods:<br/><br>
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.<br/><br>
<br/><br>
Results:<br/><br>
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.<br/><br>
<br/><br>
Conclusion:<br/><br>
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.},
  author       = {Buxbaum, Joseph D and Cai, Guiqing and Nygren, Gudrun and Chaste, Pauline and Delorme, Richard and Goldsmith, Juliet and Råstam, Maria and Silverman, Jeremy M and Hollander, Eric and Gillberg, Christopher and Leboyer, Marion and Betancur, Catalina},
  issn         = {1471-2350},
  keyword      = {Adolescent
Adult
Amino Acid Substitution/genetics*
Autistic Disorder/genetics*
Child
Child,Preschool
Craniofacial Abnormalities/genetics*
DNA Mutational Analysis
Female
Genetic Testing
Humans
Intracellular Signaling Peptides and Proteins/genetics*
Male
Nuclear Proteins/genetics*
Syndrome},
  language     = {eng},
  number       = {68},
  publisher    = {BioMed Central},
  series       = {BMC Medical Genetics},
  title        = {Mutation analysis of the NSD1 gene in patients with autism spectrum disorders and macrocephaly},
  url          = {http://dx.doi.org/10.1186/1471-2350-8-68},
  volume       = {8},
  year         = {2007},
}