title: Complex segmental duplications mediate a recurrent dup(X)(p11.22-p11.23) associated with mental retardation, speech delay, and EEG anomalies in males and females.
abstract: Submicroscopic copy-number variations make a considerable contribution to the genetic etiology of human disease. We have analyzed subjects with idiopathic mental retardation (MR) by using whole-genome oligonucleotide-based array comparative genomic hybridization (aCGH) and identified familial and de novo recurrent Xp11.22-p11.23 duplications in males and females with MR, speech delay, and a peculiar electroencephalographic (EEG) pattern in childhood. The size of the duplications ranges from 0.8-9.2 Mb. Most affected females show preferential activation of the duplicated X chromosome. Carriers of the smallest duplication show X-linked recessive inheritance. All other affected individuals present dominant expression and comparable clinical phenotypes irrespective of sex, duplication size, and X-inactivation pattern. The majority of the rearrangements are mediated by recombination between flanking complex segmental duplications. The identification of common clinical features, including the typical EEG pattern, predisposing genomic structure, and peculiar X-inactivation pattern, suggests that duplication of Xp11.22-p11.23 constitutes a previously undescribed syndrome.
authors.affiliation: Biologia Molecolare, Eugenio Medea Scientific Institute, Bosisio Parini, LC, Italy. roberto.giorda@bp.lnf.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Giorda
authors.forename: M Clara
authors.initials: MC
authors.lastname: Bonaglia
authors.forename: Silvana
authors.initials: S
authors.lastname: Beri
authors.forename: Marco
authors.initials: M
authors.lastname: Fichera
authors.forename: Francesca
authors.initials: F
authors.lastname: Novara
authors.forename: Pamela
authors.initials: P
authors.lastname: Magini
authors.forename: Jill
authors.initials: J
authors.lastname: Urquhart
authors.forename: Freddie H
authors.initials: FH
authors.lastname: Sharkey
authors.forename: Claudio
authors.initials: C
authors.lastname: Zucca
authors.forename: Rita
authors.initials: R
authors.lastname: Grasso
authors.forename: Susan
authors.initials: S
authors.lastname: Marelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Castiglia
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Benedetto
authors.forename: Sebastiano A
authors.initials: SA
authors.lastname: Musumeci
authors.forename: Girolamo A
authors.initials: GA
authors.lastname: Vitello
authors.forename: Pinella
authors.initials: P
authors.lastname: Failla
authors.forename: Santina
authors.initials: S
authors.lastname: Reitano
authors.forename: Emanuela
authors.initials: E
authors.lastname: Avola
authors.forename: Francesca
authors.initials: F
authors.lastname: Bisulli
authors.forename: Paolo
authors.initials: P
authors.lastname: Tinuper
authors.forename: Massimo
authors.initials: M
authors.lastname: Mastrangelo
authors.forename: Isabella
authors.initials: I
authors.lastname: Fiocchi
authors.forename: Luigina
authors.initials: L
authors.lastname: Spaccini
authors.forename: Claudia
authors.initials: C
authors.lastname: Torniero
authors.forename: Elena
authors.initials: E
authors.lastname: Fontana
authors.forename: Sally Ann
authors.initials: SA
authors.lastname: Lynch
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: Graeme
authors.initials: G
authors.lastname: Black
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.forename: Bernardo
authors.initials: B
authors.lastname: dalla Bernardina
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
mesh_terms: D041321:Chromosomes, Human, X / Q000235:genetics*; D004569:Electroencephalography; D005260:Female; D020440:Gene Duplication; D006801:Humans; D008607:Intellectual Disability / Q000150:complications* / Q000235:genetics*; D007805:Language Development Disorders / Q000150:complications* / Q000235:genetics*; D008297:Male; D010375:Pedigree