Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jul;11(3):291-303.
doi: 10.1007/s10048-009-0228-7. Epub 2009 Nov 18.

Novel variants identified in methyl-CpG-binding domain genes in autistic individuals

Holly N Cukier  1 , Raquel Rabionet, Ioanna Konidari, Melissa Y Rayner-Evans, Mary L Baltos, Harry H Wright, Ruth K Abramson, Eden R Martin, Michael L Cuccaro, Margaret A Pericak-Vance, John R Gilbert
Affiliations

Novel variants identified in methyl-CpG-binding domain genes in autistic individuals

Holly N Cukier et al. Neurogenetics. 2010 Jul.

Abstract

Misregulation of the methyl-CpG-binding protein 2 (MECP2) gene has been found to cause a myriad of neurological disorders including autism, mental retardation, seizures, learning disabilities, and Rett syndrome. We hypothesized that mutations in other members of the methyl-CpG-binding domain (MBD) family may also cause autistic features in individuals. We evaluated 226 autistic individuals for alterations in the four genes most homologous to MECP2: MBD1, MBD2, MBD3, and MBD4. A total of 46 alterations were identified in the four genes, including ten missense changes and two deletions that alter coding sequence. Several are either unique to our autistic population or cosegregate with affected individuals within a family, suggesting a possible relation of these variations to disease etiology. Variants include a R23M alteration in two affected half brothers which falls within the MBD domain of the MBD3 protein, as well as a frameshift in MBD4 that is predicted to truncate almost half of the protein. These results suggest that rare cases of autism may be influenced by mutations in members of the dynamic MBD protein family.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
The methyl-CpG-binding domain (MBD) protein family. The five MBD proteins, each containing an MBD domain, are illustrated. Along with this domain, each protein contains at least one other functional domain that contributes to the protein's function
Fig. 2
Fig. 2
Pedigrees of autistic families identified with mutations in MBD genes. Alterations identified in MBD1 (a–f), MBD3 (g–h), and MBD4 (i–n) are shown. Each nucleotide change is marked under the individual in whom it occurs. In families with multiple affected individuals, the initially identified autistic individual (proband) is signified with an arrow
See this image and copyright information in PMC

References

    1. Johnson CP, Myers SM. American academy of pediatrics council on children with disabilities: identification and evaluation of children with autism spectrum disorders. Pediatrics. 2007;120(5):1183–1215. - PubMed
    1. Fombonne E. Epidemiological trends in rates of autism. Mol Psychiatry. 2002;7 Suppl 2:S4–S6. - PubMed
    1. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2002 Principal Investigators, Centers for Disease Control and Prevention: prevalence of autism spectrum disorders—autism and developmental disabilities monitoring network, 14 sites, United States, 2002. MMWR Surveill Summ. 2007;56(1):12–28. - PubMed
    1. Ritvo ER, Freeman BJ, Mason-Brothers A, Mo A, Ritvo AM. Concordance for the syndrome of autism in 40 pairs of afflicted twins. Am J Psychiatry. 1985;142:74–77. - PubMed
    1. Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med. 1995;25:63–77. - PubMed

Publication types