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Evaluation of autism traits in Angelman syndrome: a resource to unfold autism genes

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Abstract

Linkage and cytogenetics studies have found the Angelman syndrome (AS) chromosomal region to be of relevance to autism disorder (AD) or autism spectrum disorder (ASD). Autism is considered part of the behavioural phenotype in AS based on formal autism assessments (autism diagnostic interview—revised [ADI-R] and autism diagnostic observation schedule [ADOS]), which have mainly addressed the deleted AS group. We explored 23 AS patients including all genetic subtypes and made a co-morbid diagnosis of AD/ASD in 14/23 (61%), which does not include 4 cases classified within the broader autism spectrum disorder (bASD). Deletions accounted for the main fraction (35%), ubiquitin-protein ligase E3A (UBE3A) mutation represented 13%, imprinting defects and uniparental disomy 9 and 4%, respectively. UBE3A mutations due to lack of the homologous to the E6-associated protein carboxyl terminus domain (n = 3) were associated with the ASD, while more distal mutations (n = 3) seem to escape from a co-morbid diagnosis of autism/autism spectrum. Differences in severity of autistic features were seen across subtypes of AS, with some behavioural features being unique to AS and some representing all forms of developmental disability. Autism signs (poor/lack of eye contact, showing, spontaneous initiation of joint attention, social quality of overtures [ADOS algorithm items for Diagnostic and Statistical Manual of Mental Disorders—IV (DSM-IV)/International Statistical Classification of Diseases and Related Health Problems—10 (ICD-10) autism diagnosis belonging to the reciprocal social interaction domain]) discriminating all the co-morbid AS categories from non-autistic AS belonged to the social interaction domain. Impairments in the communication domain (gestures, pointing, use of another’s body, frequency of vocalisation towards others [ADOS algorithm items for DSM-IV/ICD-10 autism diagnosis belonging to the communication domain]) justified classification of co-morbid AD/ASD vs the classification of less affected bASD. Evaluation of the behaviour domain suggested that repetitive sensory and motor behaviours correlate with a low developmental profile rather than being specific to autism.

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Acknowledgements

We are very thankful to the patients’ families and to the Italian Angelman Syndrome Association (ORSA) for their valuable collaboration and kindness. We would like to thank Marcello Essenziale, in Milan, and Antonio Trovato, in Troina, for videotaping and technical support. This study was partially supported by Ministry of Health, grant number: ICS 030.11-RF225 (NEMEC).

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Authors and Affiliations

  1. Clinic of Medical Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy

    Maria Teresa Bonati

  2. Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy

    Silvia Russo, Palma Finelli, Francesca Cogliati, Florinda Cavalleri & Lidia Larizza

  3. Fondazione Istituto Sacra Famiglia, Cesano Boscone, Milan, Italy

    Maria Rosa Valsecchi

  4. Autism Research Unit, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Wendy Roberts

  5. IRCCS Oasi Maria S.S., Troina, EN, Italy

    Maurizio Elia

  6. Division of Medical Genetics—San Paolo School of Medicine, University of Milan, Milan, Italy

    Lidia Larizza

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  1. Maria Teresa Bonati
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  2. Silvia Russo
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Correspondence to Maria Teresa Bonati.

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Bonati, M.T., Russo, S., Finelli, P. et al. Evaluation of autism traits in Angelman syndrome: a resource to unfold autism genes. Neurogenetics 8, 169–178 (2007). https://doi.org/10.1007/s10048-007-0086-0

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  • DOI: https://doi.org/10.1007/s10048-007-0086-0

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