title: Development of a genomic DNA reference material panel for Rett syndrome (MECP2-related disorders) genetic testing.
abstract: Rett syndrome is a dominant X-linked disorder caused by point mutations (approximately 80%) or by deletions or insertions (approximately 15% to 18%) in the MECP2 gene. It is most common in females but lethal in males, with a distinctly different phenotype. Rett syndrome patients have severe neurological and behavioral problems. Clinical genetic testing laboratories commonly use characterized genomic DNA reference materials to assure the quality of the testing process; however, none are commercially available for MECP2 genetic testing. The Centers for Disease Control and Prevention's Genetic Testing Reference Material Coordination Program, in collaboration with the genetic testing community and the Coriell Cell Repositories, established 27 new cell lines and characterized the MECP2 mutations in these and in 8 previously available cell lines. DNA samples from the 35 cell lines were tested by eight clinical genetic testing laboratories using DNA sequence analysis and methods to assess copy number (multiplex ligation-dependent probe amplification, semiquantitative PCR, or array-based comparative genomic hybridization). The eight common point mutations known to cause approximately 60% of Rett syndrome cases were identified, as were other MECP2 variants, including deletions, duplications, and frame shift and splice-site mutations. Two of the 35 samples were from males with MECP2 duplications. These MECP2 and other characterized genomic DNA samples are publicly available from the NIGMS Repository at the Coriell Cell Repositories.
authors: Laboratory Research and Evaluation Branch, Centers for Disease Control and Prevention, Atlanta, Georgia. Electronic address: lkalman@cdc.gov.
authors: Lisa V
authors: LV
authors: Kalman
authors: Fullerton Genetics Laboratory, Fullerton Genetics Center, Mission Health System, Asheville, North Carolina.
authors: Jack C
authors: JC
authors: Tarleton
authors: Intellectual and Developmental Disabilities Research Center, University of Alabama, Birmingham, Birmingham, Alabama.
authors: Alan K
authors: AK
authors: Percy
authors: Neurogenetics, GeneDx, Gaithersburg, Maryland.
authors: Swaroop
authors: S
authors: Aradhya
authors: Neurogenetics, GeneDx, Gaithersburg, Maryland.
authors: Sherri
authors: S
authors: Bale
authors: Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia.
authors: Shannon D
authors: SD
authors: Barker
authors: Molecular Genetics and Genomics Laboratory, ARUP Laboratories, Salt Lake City, Utah.
authors: Pinar
authors: P
authors: Bayrak-Toydemir
authors: Fullerton Genetics Laboratory, Fullerton Genetics Center, Mission Health System, Asheville, North Carolina.
authors: Christina
authors: C
authors: Bridges
authors: Molecular Genetics, Quest Diagnostics Nichols Institute, San Juan Capistrano, California.
authors: Arlene M
authors: AM
authors: Buller-Burckle
authors: Department of Human Genetics, University of Chicago, Chicago, Illinois.
authors: Soma
authors: S
authors: Das
authors: Molecular Genetics Laboratory, Michigan Medical Genetics Laboratories, University of Michigan Medical Center, Ann Arbor, Michigan.
authors: Ramaswamy K
authors: RK
authors: Iyer
authors: Ambry Genetics, Aliso Viejo, California.
authors: Timothy D
authors: TD
authors: Vo
authors: Molecular Genetics & Genomics, Laboratory Corporation of America, Research Triangle Park, North Carolina.
authors: Val V
authors: VV
authors: Zvereff
authors: NIGMS Human Genetic Cell Repository, Coriell Institute for Medical Research, Camden, New Jersey.
authors: Lorraine H
authors: LH
authors: Toji
mesh_terms: D002460:Cell Line; D055028:Comparative Genomic Hybridization; D005260:Female; D005820:Genetic Testing / Q000379:methods* / Q000592:standards*; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D060885:Multiplex Polymerase Chain Reaction; D012015:Reference Standards; D015518:Rett Syndrome / Q000175:diagnosis* / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D051783:Methyl-CpG-Binding Protein 2