The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders
Article first published online: 6 SEP 2001
Copyright © 2001 Wiley-Liss, Inc.
American Journal of Medical Genetics
Volume 105, Issue 8, pages 675–685, 8 December 2001
How to Cite
Bolton, P. F., Dennis, N.R., Browne, C.E., Thomas, N.S., Veltman, M.W.M., Thompson, R.J. and Jacobs, P. (2001), The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders. Am. J. Med. Genet., 105: 675–685. doi: 10.1002/ajmg.1551
- Issue published online: 23 OCT 2002
- Article first published online: 6 SEP 2001
- Manuscript Accepted: 17 APR 2001
- Manuscript Received: 31 OCT 2000
- chromosome 15;
This study investigated the phenotypic manifestations of interstitial duplications of chromosome 15 that involve the Prader-Willi/Angelman syndrome critical region (PWACR). Twenty-one affected individuals from six families were evaluated in detail, using standardized and semi-standardized measures of intelligence, psychopathology, and physical anomalies. Special attention was placed on determining the prevalence of autism spectrum disorders as well as the relationship between the parental origin of the duplication and the phenotypic effects. Assessments of the affected individuals were compared with evaluations of the unaffected relatives from the same families. Results indicated that duplications in the region were associated with variable degrees of intellectual impairments and motor coordination problems. Four of the subjects received a diagnosis of pervasive developmental disorder. Three of these cases were probands and only one met criteria for classic autism. There was very little evidence of the duplication cosegregating with autism spectrum disorder diagnosis. Paternally inherited duplications were significantly less likely to give rise to phenotypic effects. The findings indicate that duplications in the PWACR give rise to developmental delay but not necessarily autism spectrum disorders. They also suggest that phenotypic expression is dependent on the parental origin of the duplication and implicate maternally active genes in the pathogenesis of the developmental impairments. Further research will be required to clarify the range and basis of the phenotypic manifestations. © 2001 Wiley-Liss, Inc.