Copy-number variations measured by single-nucleotide-polymorphism oligonucleotide arrays in patients with mental retardation.
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.
Wagenstaller
Janine
J
Institute of Human Genetics, GSF National Research Center for Environment and Health, Munich-Neuherberg, Germany.
Spranger
Stephanie
S
Lorenz-Depiereux
Bettina
B
Kazmierczak
Bernd
B
Nathrath
Michaela
M
Wahl
Dagmar
D
Heye
Babett
B
Glaser
Dieter
D
Liebscher
Volkmar
V
Meitinger
Thomas
T
Strom
Tim M
TM
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
D017931:DNA Primers