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Phenotype–genotype correlations in 17 new patients with an Xp11.23p11.22 microduplication and review of the literature

2014; Wiley; Volume: 167; Issue: 1 Linguagem: Inglês

10.1002/ajmg.a.36807

1552-4833

Mathilde Nizon, Joris Andrieux, Caroline Rooryck, Marie‐Christine de Blois, Emilie Bourel‐Ponchel, Béatrice Bourgois, Odile Boute, Albert David, Bruno Delobel, Bénédicte Duban‐Bedu, Fabienne Giuliano, Alice Goldenberg, Sarah Grotto, Delphine Héron, Houda Karmous‐Benailly, Boris Keren, Didier Lacombe, Jean‐Michel Lapierre, Cédric Le Caignec, Eric Le Galloudec, Martine Le Merrer, Anne‐Gaëlle Le Moing, Michèle Mathieu‐Dramard, Sylvie Nusbaum, Olivier Pichon, Lucile Pinson, O Raoul, Marlène Rio, Serge Romana, A. Roubertie, Laurence Colleaux, C Turleau, Michel Vekemans, Rima Nabbout, Valérie Malan,

Glycosylation and Glycoproteins Research

Array comparative genomic hybridization (array CGH) has proven its utility in uncovering cryptic rearrangements in patients with X‐linked intellectual disability. In 2009, Giorda et al. identified inherited and de novo recurrent Xp11.23p11.22 microduplications in two males and six females from a wide cohort of patients presenting with syndromic intellectual disability. To date, 14 females and 5 males with an overlapping microduplication have been reported in the literature. To further characterize this emerging syndrome, we collected clinical and microarray data from 17 new patients, 10 females, and 7 males. The Xp11.23p11.2 microduplications detected by array CGH ranged in size from 331 Kb to 8.9 Mb. Five patients harbored 4.5 Mb recurrent duplications mediated by non‐allelic homologous recombination between segmental duplications and 12 harbored atypical duplications. The chromosomal rearrangement occurred de novo in eight patients and was inherited in six affected males from three families. Patients shared several common major characteristics including moderate to severe intellectual disability, early onset of puberty, language impairment, and age related epileptic syndromes such as West syndrome and focal epilepsy with activation during sleep evolving in some patients to continuous spikes‐and‐waves during slow sleep. Atypical microduplications allowed us to identify minimal critical regions that might be responsible for specific clinical findings of the syndrome and to suggest possible candidate genes: FTSJ1 and SHROOM4 for intellectual disability along with PQBP1 and SLC35A2 for epilepsy. Xp11.23p11.22 microduplication is a recently‐recognized syndrome associated with intellectual disability, epilepsy, and early onset of puberty in females. In this study, we propose several genes that could contribute to the phenotype. © 2014 Wiley Periodicals, Inc.