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Screening for genomic rearrangements and methylation abnormalities of the 15q11-q13 region in autism spectrum disorders
- Source :
- Biological Psychiatry, Biological Psychiatry, Elsevier, 2009, 66 (4), pp.349-59. ⟨10.1016/j.biopsych.2009.01.025⟩, Biological Psychiatry, 2009, 66 (4), pp.349-59. ⟨10.1016/j.biopsych.2009.01.025⟩
- Publication Year :
- 2009
- Publisher :
- HAL CCSD, 2009.
-
Abstract
- International audience; 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.
- Subjects :
- Male
Gene Dosage
[SDV.GEN] Life Sciences [q-bio]/Genetics
MESH: Gene Dosage
0302 clinical medicine
MESH: DNA Methylation
MESH: Child
deletion
Child
Genetics
0303 health sciences
chromosome 15
Uniparental disomy
3. Good health
MLPA
duplication
Child, Preschool
Female
Prader-Willi Syndrome
Adult
congenital, hereditary, and neonatal diseases and abnormalities
Adolescent
MESH: Autistic Disorder
autism
Biology
Dup15q
MESH: Angelman Syndrome
03 medical and health sciences
Chromosome 15
Angelman syndrome
MESH: Uniparental Disomy
Happy puppet syndrome
mental disorders
medicine
Humans
MESH: Chromosome Aberrations
Multiplex ligation-dependent probe amplification
Autistic Disorder
Biological Psychiatry
030304 developmental biology
Chromosome Aberrations
MESH: Adolescent
Chromosomes, Human, Pair 15
[SDV.GEN]Life Sciences [q-bio]/Genetics
MESH: Humans
MESH: Child, Preschool
MESH: Adult
DNA Methylation
Uniparental Disomy
medicine.disease
MESH: Male
Developmental disorder
MESH: Gene Deletion
MESH: Prader-Willi Syndrome
MESH: Microsatellite Repeats
Genomic imprinting
MESH: Female
030217 neurology & neurosurgery
Gene Deletion
Microsatellite Repeats
MESH: Chromosomes, Human, Pair 15
Subjects
Details
- Language :
- English
- ISSN :
- 00063223
- Database :
- OpenAIRE
- Journal :
- Biological Psychiatry, Biological Psychiatry, Elsevier, 2009, 66 (4), pp.349-59. ⟨10.1016/j.biopsych.2009.01.025⟩, Biological Psychiatry, 2009, 66 (4), pp.349-59. ⟨10.1016/j.biopsych.2009.01.025⟩
- Accession number :
- edsair.doi.dedup.....18e2af472c50efa67b6b4e07793efc46