Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders
| Autor: | M. Le Merrer, Laurence Colleaux, Richard Redon, Odile Raoul, Marguerite Prieur, Arnold Munnich, Jeanne Amiel, Damien Sanlaville, Delphine Héron, M-C de Blois, Nigel P. Carter, Valérie Cormier-Daire, Anne Philippe, Stanislas Lyonnet, Michel Vekemans, M-L Jacquemont |
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| Přispěvatelé: | Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
Genetic analysis MESH: Child Development Disorders Pervasive 0302 clinical medicine MESH: Child Gene duplication Chromosomes Human MESH: Syndrome Child Genetics (clinical) Oligonucleotide Array Sequence Analysis Genetics 0303 health sciences medicine.diagnostic_test MESH: Genetic Testing MESH: Genomics Genomics Syndrome 3. Good health Chromosome abnormality Medical genetics Female Original Article Adult medicine.medical_specialty Adolescent Genetic counseling Biology MESH: Chromosomes Human 03 medical and health sciences medicine Humans MESH: Chromosome Aberrations Genetic Testing 030304 developmental biology Genetic testing Chromosome Aberrations MESH: Adolescent MESH: Humans MESH: Adult medicine.disease MESH: Male Developmental disorder [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Child Development Disorders Pervasive MESH: Oligonucleotide Array Sequence Analysis Autism MESH: Female 030217 neurology & neurosurgery |
| Zdroj: | Journal of Medical Genetics Journal of Medical Genetics, BMJ Publishing Group, 2006, 43 (11), pp.843-9. ⟨10.1136/jmg.2006.043166⟩ |
| ISSN: | 0022-2593 1468-6244 |
| Popis: | Background: Autism spectrum disorders (ASD) refer to a broader group of neurobiological conditions, pervasive developmental disorders. They are characterised by a symptomatic triad associated with qualitative changes in social interactions, defect in communication abilities, and repetitive and stereotyped interests and activities. ASD is prevalent in 1 to 3 per 1000 people. Despite several arguments for a strong genetic contribution, the molecular basis of a most cases remains unexplained. About 5% of patients with autism have a chromosome abnormality visible with cytogenetic methods. The most frequent are 15q11–q13 duplication, 2q37 and 22q13.3 deletions. Many other chromosomal imbalances have been described. However, most of them remain undetectable using routine karyotype analysis, thus impeding diagnosis and genetic counselling. Methods and results: 29 patients presenting with syndromic ASD were investigated using a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Eight clinically relevant rearrangements were identified in 8 (27.5%) patients: six deletions and two duplications. Altered segments ranged in size from 1.4 to 16 Mb (2–19 clones). No recurrent abnormality was identified. Conclusion: These results clearly show that array comparative genomic hybridisation should be considered to be an essential aspect of the genetic analysis of patients with syndromic ASD. Moreover, besides their importance for diagnosis and genetic counselling, they may allow the delineation of new contiguous gene syndromes associated with ASD. Finally, the detailed molecular analysis of the rearranged regions may pave the way for the identification of new ASD genes. |
| Databáze: | OpenAIRE |
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