title: Phenotype-genotype correlations in 17 new patients with an Xp11.23p11.22 microduplication and review of the literature.
abstract: 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.
authors.affiliation: Département de Génétique, Université Paris Descartes, Sorbonne Paris Cité, Institut IMAGINE UMR_S1163, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Mathilde
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authors.lastname: Nizon
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authors.lastname: Andrieux
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authors.lastname: de Blois
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authors.lastname: Bourel-Ponchel
authors.forename: Béatrice
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authors.lastname: Giuliano
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authors.lastname: Héron
authors.forename: Houda
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authors.lastname: Karmous-Benailly
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authors.lastname: Keren
authors.forename: Didier
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authors.lastname: Lacombe
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Lapierre
authors.forename: Cédric
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authors.lastname: Le Caignec
authors.forename: Eric
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authors.lastname: Le Galloudec
authors.forename: Martine
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authors.lastname: Le Merrer
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Le Moing
authors.forename: Michèle
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authors.lastname: Mathieu-Dramard
authors.forename: Sylvie
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authors.lastname: Nusbaum
authors.forename: Olivier
authors.initials: O
authors.lastname: Pichon
authors.forename: Lucile
authors.initials: L
authors.lastname: Pinson
authors.forename: Odile
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authors.lastname: Raoul
authors.forename: Marlène
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authors.lastname: Rio
authors.forename: Serge
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authors.lastname: Romana
authors.forename: Agnès
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authors.lastname: Roubertie
authors.forename: Laurence
authors.initials: L
authors.lastname: Colleaux
authors.forename: Catherine
authors.initials: C
authors.lastname: Turleau
authors.forename: Michel
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authors.lastname: Vekemans
authors.forename: Rima
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authors.lastname: Nabbout
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authors.lastname: Malan
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D010641:Phenotype; D056916:Segmental Duplications, Genomic / Q000235:genetics*
keywords: FTSJ1; PQBP1; SLC35A2; early onset of puberty; intellectual disability; seizure