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

Roberto Giorda, M. Clara Bonaglia, Silvana Beri, Marco Fichera, Francesca Novara, Pamela Magini, Jill Urquhart, Freddie H. Sharkey, Claudio Zucca, Rita Grasso, Susan Marelli, Lucia Castiglia, Daniela Di Benedetto, Sebastiano A. Musumeci, Girolamo A. Vitello, Pinella Failla, Santina Reitano, Emanuela Avola, Francesca Bisulli, Paolo TinuperMassimo Mastrangelo, Isabella Fiocchi, Luigina Spaccini, Claudia Torniero, Elena Fontana, Sally Ann Lynch, Jill Clayton-Smith, Graeme Black, Philippe Jonveaux, Bruno Leheup, Marco Seri, Corrado Romano, Bernardo dalla Bernardina, Orsetta Zuffardi

    Research output: Contribution to journalArticlepeer-review

    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. © 2009 The American Society of Human Genetics.
    Original languageEnglish
    Pages (from-to)394-400
    Number of pages6
    JournalAmerican Journal of Human Genetics
    Volume85
    Issue number3
    DOIs
    Publication statusPublished - 11 Sept 2009

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