No association between the EN2 gene and autistic disorder
- 1Department of Pediatrics, Wayne State University, Detroit, MI 48201, USA
- 2Department of Neurology, Wayne State University, Detroit, MI 48201, USA
- Correspondence to: Dr A H M Mahbubul Huq, Division of Neurology, Children’s Hospital of Michigan, Detroit, MI 48201, USA;
A utistic spectrum disorders (MIM 209850), which include autism, Asperger syndrome, and pervasive developmental disorder (PDD) not otherwise specified, are characterised by impairment in communications and social interactions and the presence of stereotyped behaviours. The aetiology of autistic disorder is unknown, but family and twin studies have shown a high monozygotic to dizygotic twin risk ratio and a sib relative risk between 50 and 100, suggesting that inheritance of autism is complex, but the predisposition to develop it is largely genetically determined.1,2
A number of morphological abnormalities including increased brain size and developmental abnormalities of the cerebral cortex, brainstem, and cerebellum have been reported in autism.3,4 Reported brain stem and cerebellar anomalies include hypoplasia of lobules VI and VII, decreased Purkinje cell density, olivary dysplasia, and neuronal heterotopias.3–5 The morphological abnormalities described in the brainstem and cerebellum of autistic subjects suggest that genes involved in cerebellar development are candidate genes in autism.
EN2, a human homologue of Drosophila engrailed gene, is a homeobox gene with an essential role in the development of the midbrain and cerebellum.6 Mice homozygous for a targeted deletion of the EN2 homeobox region were viable but showed abnormal foliation of the cerebellum.7 Petit et al8 studied two restriction fragment length polymorphisms in the EN2 gene in autism and found an association between autism and a PvuII polymorphism in the 5′ region of EN2 in 100 autistic children and 100 control children.
In this study, we have attempted to replicate the association between the EN2 gene and autism using family based linkage and association studies in 196 multiplex families with autism. The EN2 gene maps to human chromosome 7q36. Information regarding a number of promoter, exon, and intron polymorphisms in the EN2 gene is available in …