title: Screening for genomic rearrangements and methylation abnormalities of the 15q11-q13 region in autism spectrum disorders.
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).
  
  
  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.
authors.affiliation: INSERM U679, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Depienne
authors.forename: Daniel
authors.initials: D
authors.lastname: Moreno-De-Luca
authors.forename: Delphine
authors.initials: D
authors.lastname: Heron
authors.forename: Delphine
authors.initials: D
authors.lastname: Bouteiller
authors.forename: Aurélie
authors.initials: A
authors.lastname: Gennetier
authors.forename: Richard
authors.initials: R
authors.lastname: Delorme
authors.forename: Pauline
authors.initials: P
authors.lastname: Chaste
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Siffroi
authors.forename: Sandra
authors.initials: S
authors.lastname: Chantot-Bastaraud
authors.forename: Baya
authors.initials: B
authors.lastname: Benyahia
authors.forename: Oriane
authors.initials: O
authors.lastname: Trouillard
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nygren
authors.forename: Svenny
authors.initials: S
authors.lastname: Kopp
authors.forename: Maria
authors.initials: M
authors.lastname: Johansson
authors.forename: Maria
authors.initials: M
authors.lastname: Rastam
authors.forename: Lydie
authors.initials: L
authors.lastname: Burglen
authors.forename: Eric
authors.initials: E
authors.lastname: Leguern
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Christopher
authors.initials: C
authors.lastname: Gillberg
authors.forename: Catalina
authors.initials: C
authors.lastname: Betancur
mesh_terms: D000293:Adolescent; D000328:Adult; D017204:Angelman Syndrome / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D011218:Prader-Willi Syndrome / Q000235:genetics; D024182:Uniparental Disomy