title: Novel variants identified in methyl-CpG-binding domain genes in autistic individuals.
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.
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL 33136, USA.
authors.forename: Holly N
authors.initials: HN
authors.lastname: Cukier
authors.forename: Raquel
authors.initials: R
authors.lastname: Rabionet
authors.forename: Ioanna
authors.initials: I
authors.lastname: Konidari
authors.forename: Melissa Y
authors.initials: MY
authors.lastname: Rayner-Evans
authors.forename: Mary L
authors.initials: ML
authors.lastname: Baltos
authors.forename: Harry H
authors.initials: HH
authors.lastname: Wright
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Abramson
authors.forename: Eden R
authors.initials: ER
authors.lastname: Martin
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cuccaro
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: John R
authors.initials: JR
authors.lastname: Gilbert
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000235:genetics*; D004706:Endodeoxyribonucleases / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D020125:Mutation, Missense; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C066141:MBD1 protein, human; C115368:MBD2 protein; C115369:MBD3 protein, human; D051783:Methyl-CpG-Binding Protein 2; D014157:Transcription Factors; D004706:Endodeoxyribonucleases; C118712:MBD4 protein, human