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Delineation of MidXq28-duplication syndrome distal to MECP2 and proximal to RAB39B genes |
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| Authors: | Lorenzo Sinibaldi Valentina Parisi Silvia Lanciotti Paolo Fontana Alma Kuechler Genevieve Baujat Barbara Torres Judith Koetting Alessandra Splendiani Diana Postorivo Jasmin Beygo Francesco G. Garaci Valerie Malan Hermann-Josef Lüdecke Valentina Guida Mandy Krumbiegel Fortunato Lonardo Antonio Novelli Beate Albrecht Chiara Perria Gioacchino Scarano Malte Spielmann Annamaria M. Nardone Agatino Battaglia Francesco Brancati Laura Bernardini |
| Affiliation: | 1. Medical Genetics Unit, Bambino Gesù Pediatric Hospital IRCCS, Rome, Italy;2. Medical Genetics Unit, Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo (FG), Italy;3. Medical Genetics Residency Programme, Tor Vergata University, Rome, Italy;4. Medical Genetics Unit, A.O.R.N. San Pio, Benevento, Italy;5. Universitätsklinikum Essen, Essen, Germany;6. Department of Genetics, Necker-Enfants Malades Hospital, Paris, France;7. Neuroradiology Unit, University of L'Aquila, L'Aquila, Italy;8. Medical Genetics Unit, Policlinico Tor Vergata, Rome, Italy;9. Neuroradiology, Department of Biomedicine and Prevention, Tor Vergata University Rome, Rome, Italy San Raffaele Cassino, Cassino, Italy;10. Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany;11. Medical Genetics Laboratory, Bambino Gesù Pediatric Hospital IRCCS, Rome, Italy;12. Childhood and Adolescence Neuropsychiatry Section, University of Sassari, Sassari, Italy;13. Human Molecular Genomics Group, Max Planck Institute for Molecular Genetics, Berlin, Germany;14. Department of Developmental Neuroscience, IRCCS “Stella Maris Foundation”, Pisa, Italy;15. Medical Genetics Residency Programme, Tor Vergata University, Rome, Italy Human Genetics Institute, Life, Health, Environmental Sciences Department, University of L'Aquila, Italy Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy |
| Abstract: | Two distinct genomic disorders have been linked to Xq28-gains, namely Xq28-duplications including MECP2 and Int22h1/Int22h2-mediated duplications involving RAB39B. Here, we describe six unrelated patients, five males and one female, with Xq28-gains distal to MECP2 and proximal to the Int22h1/Int22h2 low copy repeats. Comparison with patients carrying overlapping duplications in the literature defined the MidXq28-duplication syndrome featuring intellectual disability, language impairment, structural brain malformations, microcephaly, seizures and minor craniofacial features. The duplications overlapped for 108 kb including FLNA, RPL10 and GDI1 genes, highly expressed in brain and candidates for the neurologic phenotype. |
| Keywords: | corpus callosum and cerebellar vermis hypoplasia developmental delay/intellectual disability microcephaly Xq28-duplication |