title: Copy-number variations measured by single-nucleotide-polymorphism oligonucleotide arrays in patients with mental retardation.
abstract: Whole-genome analysis using high-density single-nucleotide-polymorphism oligonucleotide arrays allows identification of microdeletions, microduplications, and uniparental disomies. We studied 67 children with unexplained mental retardation with normal karyotypes, as assessed by G-banded chromosome analyses. Their DNAs were analyzed with Affymetrix 100K arrays. We detected 11 copy-number variations that most likely are causative of mental retardation, because they either arose de novo (9 cases) and/or overlapped with known microdeletions (2 cases). The eight deletions and three duplications varied in size from 200 kb to 7.5 Mb. Of the 11 copy-number variations, 5 were flanked by low-copy repeats. Two of those, on chromosomes 15q25.2 and Xp22.31, have not been described before and have a high probability of being causative of new deletion and duplication syndromes, respectively. In one patient, we found a deletion affecting only a single gene, MBD5, which codes for the methyl-CpG-binding domain protein 5. In addition to the 67 children, we investigated 4 mentally retarded children with apparent balanced translocations and detected four deletions at breakpoint regions ranging in size from 1.1 to 14 Mb.
authors.affiliation: Institute of Human Genetics, GSF National Research Center for Environment and Health, Munich-Neuherberg, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Wagenstaller
authors.forename: Stephanie
authors.initials: S
authors.lastname: Spranger
authors.forename: Bettina
authors.initials: B
authors.lastname: Lorenz-Depiereux
authors.forename: Bernd
authors.initials: B
authors.lastname: Kazmierczak
authors.forename: Michaela
authors.initials: M
authors.lastname: Nathrath
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wahl
authors.forename: Babett
authors.initials: B
authors.lastname: Heye
authors.forename: Dieter
authors.initials: D
authors.lastname: Glaser
authors.forename: Volkmar
authors.initials: V
authors.lastname: Liebscher
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D020440:Gene Duplication; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers