title: X-chromosome duplications in males with mental retardation: pathogenic or benign variants?
abstract: Studies to identify copy number variants (CNVs) on the X-chromosome have revealed novel genes important in the causation of X-linked mental retardation (XLMR). Still, for many CNVs it is unclear whether they are associated with disease or are benign variants. We describe six different CNVs on the X-chromosome in five male patients with mental retardation that were identified by conventional karyotyping and single nucleotide polymorphism array analysis. One deletion and five duplications ranging in size from 325 kb to 12.5 Mb were observed. Five CNVs were maternally inherited and one occurred de novo. We discuss the involvement of potential candidate genes and focus on the complexity of X-chromosomal duplications in males inherited from healthy mothers with different X-inactivation patterns. Based on size and/or the presence of XLMR genes we were able to classify CNVs as pathogenic in two patients. However, it remains difficult to decide if the CNVs in the other three patients are pathogenic or benign.
authors.affiliation: Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Einthovenweg 20, Leiden, The Netherlands. a.c.j.gijsbers@lumc.nl
authors.forename: A C J
authors.initials: AC
authors.lastname: Gijsbers
authors.forename: N S
authors.initials: NS
authors.lastname: den Hollander
authors.forename: A T J M
authors.initials: AT
authors.lastname: Helderman-van de Enden
authors.forename: J H M
authors.initials: JH
authors.lastname: Schuurs-Hoeijmakers
authors.forename: L
authors.initials: L
authors.lastname: Vijfhuizen
authors.forename: E K
authors.initials: EK
authors.lastname: Bijlsma
authors.forename: A
authors.initials: A
authors.lastname: van Haeringen
authors.forename: K B M
authors.initials: KB
authors.lastname: Hansson
authors.forename: E
authors.initials: E
authors.lastname: Bakker
authors.forename: M H
authors.initials: MH
authors.lastname: Breuning
authors.forename: C A L
authors.initials: CA
authors.lastname: Ruivenkamp
mesh_terms: D015139:Blotting, Southern; D058674:Chromosome Duplication; D041321:Chromosomes, Human, X; D018628:Gene Dosage; D006801:Humans; D007621:Karyotyping; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D017384:Sequence Deletion; D049951:X Chromosome Inactivation / Q000235:genetics*