Advanced

Screening for Genomic Rearrangements and Methylation Abnormalities of the 15q11-q13 Region in Autism Spectrum Disorders

Depienne, Christel; Moreno-De-Luca, Daniel; Heron, Delphine; Bouteiller, Delphine; Gennetier, Aurélie; Delorme, Richard; Chaste, Pauline; Siffroi, Jean-Pierre; Chantot-Bastaraud, Sandra and Benyahia, Baya, et al. (2009) In Biological Psychiatry 66(4). p.349-359
Abstract
BACKGROUND: Maternally derived duplications of the 15q11-q13 region are the most frequently reported chromosomal aberrations in autism spectrum disorders (ASD).Prader-Willi and Angelman syndromes, caused by 15q11-q13 deletions or abnormal methylation of imprinted genes, are also associated with ASD. However, the prevalence of these disorders in ASD is unknown. The aim of this study was to assess the frequency of 15q11-q13 rearrangements in a large sample of patients ascertained for ASD.



METHODS: A total of 522 patients belonging to 430 families were screened for deletions, duplications, and methylation abnormalities involving 15q11-q13 with multiplex ligation-dependent probe amplification (MLPA).



... (More)
BACKGROUND: Maternally derived duplications of the 15q11-q13 region are the most frequently reported chromosomal aberrations in autism spectrum disorders (ASD).Prader-Willi and Angelman syndromes, caused by 15q11-q13 deletions or abnormal methylation of imprinted genes, are also associated with ASD. However, the prevalence of these disorders in ASD is unknown. The aim of this study was to assess the frequency of 15q11-q13 rearrangements in a large sample of patients ascertained for ASD.



METHODS: A total of 522 patients belonging to 430 families were screened for deletions, duplications, and methylation abnormalities involving 15q11-q13 with multiplex ligation-dependent probe amplification (MLPA).



RESULTS: We identified four patients with 15q11-q13 abnormalities: a supernumerary chromosome 15, a paternal interstitial duplication, and two subjects with Angelman syndrome, one with a maternal deletion and the other with a paternal uniparental disomy.



CONCLUSIONS: Our results show that abnormalities of the 15q11-q13 region are a significant cause of ASD, accounting for approximately 1% of cases. Maternal interstitial 15q11-q13 duplications, previously reported to be present in 1% of patients with ASD, were not detected in our sample. Although paternal duplications of chromosome 15 remain phenotypically silent in the majority of patients, they can give rise to developmental delay and ASD in some subjects, suggesting that paternally expressed genes in this region can contribute to ASD, albeit with reduced penetrance compared with maternal duplications. These findings indicate that patients with ASD should be routinely screened for 15q genomic imbalances and methylation abnormalities and that MLPA is a reliable, rapid, and cost-effective method to perform this screening. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
MLPA, Autism, chromosome 15, duplication, deletion, Angelman syndrome
in
Biological Psychiatry
volume
66
issue
4
pages
349 - 359
publisher
Society of Biological Psychiatry Published by Elsevier Inc.
external identifiers
  • scopus:67651183634
ISSN
0006-3223
DOI
10.1016/j.biopsych.2009.01.025
language
English
LU publication?
yes
id
1e9f4f25-dc9c-4e37-a506-66d731181b00 (old id 1430893)
date added to LUP
2011-02-18 15:07:09
date last changed
2017-08-20 04:45:53
@article{1e9f4f25-dc9c-4e37-a506-66d731181b00,
  abstract     = {BACKGROUND: Maternally derived duplications of the 15q11-q13 region are the most frequently reported chromosomal aberrations in autism spectrum disorders (ASD).Prader-Willi and Angelman syndromes, caused by 15q11-q13 deletions or abnormal methylation of imprinted genes, are also associated with ASD. However, the prevalence of these disorders in ASD is unknown. The aim of this study was to assess the frequency of 15q11-q13 rearrangements in a large sample of patients ascertained for ASD. <br/><br>
<br/><br>
METHODS: A total of 522 patients belonging to 430 families were screened for deletions, duplications, and methylation abnormalities involving 15q11-q13 with multiplex ligation-dependent probe amplification (MLPA). <br/><br>
<br/><br>
RESULTS: We identified four patients with 15q11-q13 abnormalities: a supernumerary chromosome 15, a paternal interstitial duplication, and two subjects with Angelman syndrome, one with a maternal deletion and the other with a paternal uniparental disomy. <br/><br>
<br/><br>
CONCLUSIONS: Our results show that abnormalities of the 15q11-q13 region are a significant cause of ASD, accounting for approximately 1% of cases. Maternal interstitial 15q11-q13 duplications, previously reported to be present in 1% of patients with ASD, were not detected in our sample. Although paternal duplications of chromosome 15 remain phenotypically silent in the majority of patients, they can give rise to developmental delay and ASD in some subjects, suggesting that paternally expressed genes in this region can contribute to ASD, albeit with reduced penetrance compared with maternal duplications. These findings indicate that patients with ASD should be routinely screened for 15q genomic imbalances and methylation abnormalities and that MLPA is a reliable, rapid, and cost-effective method to perform this screening.},
  author       = {Depienne, Christel and Moreno-De-Luca, Daniel and Heron, Delphine and Bouteiller, Delphine and Gennetier, Aurélie and Delorme, Richard and Chaste, Pauline and Siffroi, Jean-Pierre and Chantot-Bastaraud, Sandra and Benyahia, Baya and Trouillard, Oriane and Nygren, Gudrun and Kopp, Svenny and Johansson, Maria and Råstam, Maria and Burglen, Lydie and Leguern, Eric and Verloes, Alain and Leboyer, Marion and Brice, Alexis and Gillberg, Christopher and Betancur, Catalina},
  issn         = {0006-3223},
  keyword      = {MLPA,Autism,chromosome 15,duplication,deletion,Angelman syndrome},
  language     = {eng},
  number       = {4},
  pages        = {349--359},
  publisher    = {Society of Biological Psychiatry Published by Elsevier Inc.},
  series       = {Biological Psychiatry},
  title        = {Screening for Genomic Rearrangements and Methylation Abnormalities of the 15q11-q13 Region in Autism Spectrum Disorders},
  url          = {http://dx.doi.org/10.1016/j.biopsych.2009.01.025},
  volume       = {66},
  year         = {2009},
}