Phenotype-genotype correlations in 17 new patients with an Xp11.23p11.22 microduplication and review of the literature.
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.
['Nizon|Mathilde|M|', 'Andrieux|Joris|J|', 'Rooryck|Caroline|C|', 'de Blois|Marie-Christine|MC|', 'Bourel-Ponchel|Emilie|E|', 'Bourgois|Béatrice|B|', 'Boute|Odile|O|', 'David|Albert|A|', 'Delobel|Bruno|B|', 'Duban-Bedu|Bénédicte|B|', 'Giuliano|Fabienne|F|', 'Goldenberg|Alice|A|', 'Grotto|Sarah|S|', 'Héron|Delphine|D|', 'Karmous-Benailly|Houda|H|', 'Keren|Boris|B|', 'Lacombe|Didier|D|', 'Lapierre|Jean-Michel|JM|', 'Le Caignec|Cédric|C|', 'Le Galloudec|Eric|E|', 'Le Merrer|Martine|M|', 'Le Moing|Anne-Gaëlle|AG|', 'Mathieu-Dramard|Michèle|M|', 'Nusbaum|Sylvie|S|', 'Pichon|Olivier|O|', 'Pinson|Lucile|L|', 'Raoul|Odile|O|', 'Rio|Marlène|M|', 'Romana|Serge|S|', 'Roubertie|Agnès|A|', 'Colleaux|Laurence|L|', 'Turleau|Catherine|C|', 'Vekemans|Michel|M|', 'Nabbout|Rima|R|', 'Malan|Valérie|V|']
D000293:Adolescent D000328:Adult D002648:Child D002675:Child, Preschool D002874:Chromosome Mapping D041321:Chromosomes, Human, X D055028:Comparative Genomic Hybridization D004569:Electroencephalography D004827:Epilepsy D005260:Female D056726:Genetic Association Studies D006801:Humans D008297:Male D010641:Phenotype D056916:Segmental Duplications, Genomic
intellectual disability early onset of puberty FTSJ1 PQBP1 SLC35A2 seizure