1. ¹Center for Epidemiology and Biostatistics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati, OH, USA
2. ²Division of Developmental Disabilities, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati, OH, USA
3. ³Division of Human Genetics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati, OH, USA

Correspondence: CA Molloy, MD, MS, Center for Epidemiology and Biostatistics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 5041, Cincinnati, OH 45229-3039, USA. E-mail: Cynthia.molloy@cchmc.org

Received 20 January 2005; Revised 4 March 2005; Accepted 5 April 2005; Published online 10 May 2005.

Abstract

Autism is a pervasive developmental disorder with a strong genetic component. While candidate regions of the genome have been identified, location of genes conferring susceptibility to autism has been hindered by the heterogeneity within this clinically defined disorder, and the likely contribution of many genes of weak effect. Subsetting samples on the basis of distinct, nondiagnostic clinical features has been recommended to decrease sample heterogeneity. In this study, linkage analysis was performed on a subset of families in the database of the Autism Genetic Resource Exchange (AGRE). This set of autism-affected relative pairs (n=34) was also concordant for a history of developmental regression as measured by the Autism Diagnostic Interview—Revised (ADI-R). In this sample, a maximum multipoint LOD score of 3.4 under the dominant mode of inheritance and an NPL score of 3.0 (P=1.3 10^-3) were observed on chromosome 21 near D21S1437. On chromosome 7 near D7S483 a LOD score of 2.0 under the dominant mode of inheritance and an NPL score of 3.7 (P=7.9 10^-5) were observed. Genetic elements in these regions of 21q and 7q are likely to confer susceptibility to autism or modify the disease presentation in a subgroup of children characterized by a history of developmental regression.