title: Additional cryptic CNVs in mentally retarded patients with apparently balanced karyotypes.
abstract: Apparently balanced chromosome abnormalities are occasionally associated with mental retardation (MR). These balanced rearrangements may disrupt genes. However, the phenotype may also be caused by small abnormalities present at the breakpoints or elsewhere in the genome. Conventional karyotyping is not instrumental for detecting small abnormalities because it only identifies genomic imbalances larger than 5-10 Mb. In contrast, high-resolution whole-genome arrays enable the detection of submicroscopic abnormalities in patients with apparently balanced rearrangements. Here, we report on the whole-genome analysis of 13 MR patients with previously detected balanced chromosomal abnormalities, five de novo, four inherited, and four of unknown inheritance, using Single Nucleotide Polymorphism (SNP) arrays. In all the cases, the patient had an abnormal phenotype. In one familial case and one unknown inheritance case, one of the parents had a phenotype which appeared identical to the patient's phenotype. Additional copy number variants (CNVs) were identified in eight patients. Three patients contained CNVs adjacent to one or either breakpoints. One of these patients showed four and two deletions near the breakpoints of a de novo pericentric inversion. In five patients we identified CNVs on chromosomes unrelated to the previously observed genomic imbalance. These data demonstrate that high-resolution array screening and conventional karyotyping is necessary to tie complex karyotypes to phenotypes of MR patients.
authors.affiliation: Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, the Netherlands. a.c.j.gijsbers@lumc.nl
authors.forename: Antoinet C J
authors.initials: AC
authors.lastname: Gijsbers
authors.forename: Cathy A J
authors.initials: CA
authors.lastname: Bosch
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Dauwerse
authors.forename: Osdilly
authors.initials: O
authors.lastname: Giromus
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hansson
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hilhorst-Hofstee
authors.forename: Marjolein
authors.initials: M
authors.lastname: Kriek
authors.forename: Arie
authors.initials: A
authors.lastname: van Haeringen
authors.forename: Emilia K
authors.initials: EK
authors.lastname: Bijlsma
authors.forename: Egbert
authors.initials: E
authors.lastname: Bakker
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.forename: Claudia A L
authors.initials: CA
authors.lastname: Ruivenkamp
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002675:Child, Preschool; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D056915:DNA Copy Number Variations; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014178:Translocation, Genetic