Copy-Number Variations Measured by Single-Nucleotide–Polymorphism Oligonucleotide Arrays in Patients with Mental Retardation

• Published in: American journal of human genetics Vol. 81; no. 4; pp. 768 - 779
• Main Authors: Wagenstaller, Janine, Spranger, Stephanie, Lorenz-Depiereux, Bettina, Kazmierczak, Bernd, Nathrath, Michaela, Wahl, Dagmar, Heye, Babett, Gläser, Dieter, Liebscher, Volkmar, Meitinger, Thomas, Strom, Tim M.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.10.2007; University of Chicago Press; Cell Press; American Society of Human Genetics
• Subjects: Adult and adolescent clinical studies; Base Sequence; Biological and medical sciences; Child; Child, Preschool; Children & youth; Chromosomes; Craniofacial Abnormalities - genetics; Craniofacial Abnormalities - pathology; Deoxyribonucleic acid; DNA; DNA Primers - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Dosage; Gene Duplication; General aspects. Genetic counseling; Genes; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Genomics; Humans; Infant; Intellectual deficiency; Intellectual Disability - genetics; Intellectual Disability - pathology; Male; Medical genetics; Medical sciences; Mental retardation; Molecular and cellular biology; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; Phenotype; Polymorphism, Single Nucleotide; Proteins; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Syndrome; Translocation, Genetic; Human; Copy number; Intellectual deficiency; Variations; Genetics; Patient; Developmental disorder; Oligonucleotide; Single nucleotide polymorphism; Mental retardation
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/521274

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.