Genotype–phenotype analysis of 18q12.1-q12.2 copy number variation in autism
| Autor: | Christine Tyson, Joris Andrieux, Xudong Liu, Peter T. C. Wang, Evica Rajcan-Separovic, E. Lopez-Rangel, Prescilla Carrion, Göran Annerén, Kristina Calli, Ann-Charlotte Thuresson, Bruno Delobel, Ying Qiao, M. E. Suzanne Lewis, Monica Hrynchak, Bénédicte Duban-Bedu |
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| Rok vydání: | 2013 |
| Předmět: |
Candidate gene
DNA Copy Number Variations Trisomy Biology Short stature 03 medical and health sciences 0302 clinical medicine Gene duplication Intellectual disability Genetics medicine Humans Copy-number variation Child 10. No inequality Genetic Association Studies Genetics (clinical) 030304 developmental biology Comparative Genomic Hybridization 0303 health sciences Genetic heterogeneity Facies General Medicine medicine.disease Hypotonia Child Development Disorders Pervasive Autism Female medicine.symptom Chromosomes Human Pair 18 030217 neurology & neurosurgery |
| Zdroj: | European Journal of Medical Genetics. 56:420-425 |
| ISSN: | 1769-7212 |
| DOI: | 10.1016/j.ejmg.2013.05.006 |
| Popis: | Autism Spectrum Disorders (ASD) are complex neurodevelopmental conditions characterized by delays in social interactions and communication as well as displays of restrictive/repetitive interests. DNA copy number variants have been identified as a genomic susceptibility factor in ASDs and imply significant genetic heterogeneity. We report a 7-year-old female with ADOS-G and ADI-R confirmed autistic disorder harbouring a de novo 4 Mb duplication (18q12.1). Our subject displays severely deficient expressive language, stereotypic and repetitive behaviours, mild intellectual disability (ID), focal epilepsy, short stature and absence of significant dysmorphic features. Search of the PubMed literature and DECIPHER database identified 4 additional cases involving 18q12.1 associated with autism and/or ID that overlap our case: one duplication, two deletions and one balanced translocation. Notably, autism and ID are seen with genomic gain or loss at 18q12.1, plus epilepsy and short stature in duplication cases, and hypotonia and tall stature in deletion cases. No consistent dysmorphic features were noted amongst the reviewed cases. We review prospective ASD/ID candidate genes integral to 18q12.1, including those coding for the desmocollin/desmoglein cluster, ring finger proteins 125 and 138, trafficking protein particle complex 8 and dystrobrevin-alpha. The collective clinical and molecular features common to microduplication 18q12.1 suggest that dosage-sensitive, position or contiguous gene effects may be associated in the etiopathogenesis of this autism-ID-epilepsy syndrome. |
| Databáze: | OpenAIRE |
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