title: Molecular karyotyping of patients with unexplained mental retardation by SNP arrays: a multicenter study.
abstract: Genomic microarrays have been implemented in the diagnosis of patients with unexplained mental retardation. This method, although revolutionizing cytogenetics, is still limited to the detection of rare de novo copy number variants (CNVs). Genome-wide single nucleotide polymorphism (SNP) microarrays provide high-resolution genotype as well as CNV information in a single experiment. We hypothesize that the widespread use of these microarray platforms can be exploited to greatly improve our understanding of the genetic causes of mental retardation and many other common disorders, while already providing a robust platform for routine diagnostics. Here we report a detailed validation of Affymetrix 500k SNP microarrays for the detection of CNVs associated to mental retardation. After this validation we applied the same platform in a multicenter study to test a total of 120 patients with unexplained mental retardation and their parents. Rare de novo CNVs were identified in 15% of cases, showing the importance of this approach in daily clinical practice. In addition, much more genomic variation was observed in these patients as well as their parents. We provide all of these data for the scientific community to jointly enhance our understanding of these genomic variants and their potential role in this common disorder.
authors.affiliation: West Midlands Regional Genetics Laboratory and Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham, United Kingdom.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: McMullan
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Jayne Y
authors.initials: JY
authors.lastname: Hehir-Kwa
authors.forename: Bert B A
authors.initials: BB
authors.lastname: de Vries
authors.forename: Andreas
authors.initials: A
authors.lastname: Dufke
authors.forename: Eleanor
authors.initials: E
authors.lastname: Rattenberry
authors.forename: Marloes
authors.initials: M
authors.lastname: Steehouwer
authors.forename: Luminita
authors.initials: L
authors.lastname: Moruz
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.forename: Nicole
authors.initials: N
authors.lastname: de Leeuw
authors.forename: Angelika
authors.initials: A
authors.lastname: Riess
authors.forename: Ozge
authors.initials: O
authors.lastname: Altug-Teber
authors.forename: Herbert
authors.initials: H
authors.lastname: Enders
authors.forename: Sylke
authors.initials: S
authors.lastname: Singer
authors.forename: Ute
authors.initials: U
authors.lastname: Grasshoff
authors.forename: Michael
authors.initials: M
authors.lastname: Walter
authors.forename: Judith M
authors.initials: JM
authors.lastname: Walker
authors.forename: Catherine V
authors.initials: CV
authors.lastname: Lamb
authors.forename: E Val
authors.initials: EV
authors.lastname: Davison
authors.forename: Louise
authors.initials: L
authors.lastname: Brueton
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Joris A
authors.initials: JA
authors.lastname: Veltman
mesh_terms: D018628:Gene Dosage; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011933:Reagent Kits, Diagnostic / Q000592:standards; D024182:Uniparental Disomy
chemical_list: D011933:Reagent Kits, Diagnostic