Methyl-CpG binding protein 2 gene (MECP2), the gene implicated in Rett syndrome, was also reported to be involved in mental retardation and autism. MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a nuclear protein family sharing the methyl-CpG binding domain (MBD) and are related to transcriptional repression. In 65 Japanese autistic patients, all the exons of each gene were screened for mutations by DHPLC, and the results were confirmed by direct sequencing. An R269C mutation that resulted in the addition of cysteine near a cysteine rich region was found in the MBD1 gene in one patient. This mutation was also detected in the patient's father with some phenotypes of autism and his normal sister, but not in 151 controls. Two repeat length polymorphisms, (GGGGCC)2 to 3 and (GGC)4 to 5, were detected in MBD2, and several polymorphisms were detected in each gene. Although our findings could not confirm that the genes of this family are responsible for the etiology in the majority of autistic patients, the R269C mutation in the MBD1 gene may relate to autism. The potential association of the high-polymorphic gene variants with autism needs to be studied further. Furthermore, these polymorphisms are useful for linkage analysis.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Brain and Development
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism.Nat Genet. 2003; 34: 27-29
- Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.Nat Genet. 1999; 23: 185-188
- Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome.J Med Genet. 2000; 37: E41
- Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes.Mamm Genome. 1999; 10: 906-912
- Methyl-CpG-binding proteins. Targeting specific gene repression.Eur J Biochem. 2001; 268: 1-6
- Identification and characterization of a family of mammalian methyl-CpG binding proteins.Mol Cell Biol. 1998; 18: 6538-6547
- Neuropsychiatry of 18q− syndrome.Am J Med Genet. 1996; 67: 172-178
- Mutation analysis of the coding sequence of the MECP2 gene in infantile autism.Hum Genet. 2002; 111: 305-309
- Mechanism of transcriptional regulation by methyl-CpG binding protein MBD1.Mol Cell Biol. 2000; 20: 5107-5118
- Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function.Proc Natl Acad Sci USA. 2003; 100: 6777-6782
- Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development.Genes Dev. 2001; 15: 710-723
Accepted: August 10, 2004
Received: July 6, 2004
© 2004 Published by Elsevier Inc.