Journal of Genetics

, 98:10 | Cite as

Spectrum of X-linked intellectual disabilities and psychiatric symptoms in a family harbouring a Xp22.12 microduplication encompassing the RPS6KA3 gene

  • Vera Uliana
  • Francesco Bonatti
  • Valentina Zanatta
  • Paola Mozzoni
  • Davide Martorana
  • Antonio PercesepeEmail author
Research Note


Microduplications of the X chromosome are a rare cause of X-linked intellectual disability (XLID), a clinically and genetically heterogeneous spectrum of disorders. In the present study, a 950-kb Xp22.12 microduplication including the RPS6KA3 gene was detected in affected members of a family, including the proband (male), his mother and one maternal uncle. Four female carriers had major depression and one of them also had mild intellectual disability. The present and previous cases with overlapping microduplications suggest that Xp22.12 microduplications can be included in the neuropsychiatric copy number variations.


Xp22.12 microduplication RPS6KA3 gene X-linked intellectual disabilities 



This work was supported by the ‘Fondazione Emma ed Ernesto Rulfo per la Genetica Medica’ (Italy). This study makes used of data generated by the DECIPHER Consortium. We are indebted to the family members for their collaboration.


  1. Bertini V., Cambi F., Bruno R., Toschi B., Forli F., Berrettini S. et al. 2015 625 kb microduplication at Xp22.12 including RPS6KA3 in a child with mild intellectual disability. J. Hum. Genet. 60, 777–780.CrossRefGoogle Scholar
  2. Field M., Tarpey P., Boyle J., Edkins S., Goodship J., Luo Y. et al. 2006 Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation. Clin. Genet70, 509–515.CrossRefGoogle Scholar
  3. Gécz J., Shoubridge C. and Corbett M. 2009 The genetic landscape of intellectual disability arising from chromosome X. Trends Genet. 25, 308--316.CrossRefGoogle Scholar
  4. Hauge C. and Frödin M. 2006 RSK and MSK in MAP kinase signalling. J. Cell Sci119, 3021–3023.CrossRefGoogle Scholar
  5. Jacquot S., Zeniou M., Touraine R. and Hanauer A. 2002 X-linked Coffin-Lowry syndrome (CLS, MIM 303600, RPS6KA3 gene, protein product known under various names: pp90(rsk2), RSK2, ISPK, MAPKAP1). Eur. J. Hum. Genet10, 2–5.CrossRefGoogle Scholar
  6. Koolen D. A., Kramer J. M., Neveling K., Nillesen W. M., Moore-Barton H. L., Elmslie F. V. et al. 2012 Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. Nat. Genet. 44, 639–641.CrossRefGoogle Scholar
  7. Madrigal I., Rodríguez-Revenga L., Armengol L., González E., Rodriguez B., Badenas C. et al. 2007 X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation. BMC Genomics 8, 443.CrossRefGoogle Scholar
  8. Manouvrier-Hanu S., Amiel J., Jacquot S., Merienne K., Moerman A., Coëslier A. et al. 1999 Unreported RSK2 missense mutation in two male sibs with an unusually mild form of Coffin-Lowry syndrome. J. Med. Genet. 36, 775–778.CrossRefGoogle Scholar
  9. Matsumoto A., Kuwajima M., Miyake K., Kojima K., Nakashima N., Jimbo E. F. et al. 2013 An Xp22.12 microduplication including RPS6KA3 identified in a family with variably affected intellectual and behavioral disabilities. J. Hum. Genet. 58, 755–757.CrossRefGoogle Scholar
  10. Merienne K., Jacquot S., Pannetier S., Zeniou M., Bankier A., Gecz J. et al. 1999 A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation. Nat. Genet. 22, 13–14.CrossRefGoogle Scholar
  11. Pereira M. P., Heron D. and Hanauer A. 2007 The first large duplication of the RSK2 gene identified in a Coffin-Lowry syndrome patient. Hum. Genet. 122, 541--543.CrossRefGoogle Scholar
  12. Pereira P. M., Schneider A., Pannetier S., Heron D. and Hanauer A. 2010 Coffin-Lowry syndrome. Eur. J. Hum. Genet. 18, 627--633.CrossRefGoogle Scholar
  13. Potocki L., Bi W., Treadwell-Deering D., Carvalho C. M., Eifert A., Friedman E. M. et al. 2007 Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage- sensitive critical interval that can convey an autism phenotype. Am. J. Hum. Genet. 80, 633–649.CrossRefGoogle Scholar
  14. Stefansson H., Meyer-Lindenberg A., Steinberg S., Magnusdottir B., Morgen K., Arnarsdottir S. et al. 2014 CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature 505, 361–366.CrossRefGoogle Scholar
  15. Tejada M. I., Martínez-Bouzas C., García-Ribes A., Larrucea S., Acquadro F., Cigudosa J. C. et al. 2011 A child with mild X-linked intellectual disability and a microduplication at Xp22.12 including RPS6KA3. Pediatrics 128, e1029–1033.CrossRefGoogle Scholar
  16. Tzschach A., Chen W., Erdogan F., Hoeller A., Ropers H. H., Castellan C. et al. 2008 Characterization of interstitial Xp duplications in two families by tiling path array CGH. Am. J. Med. Genet. A 46, 197–203.CrossRefGoogle Scholar
  17. Uliana V. and Percesepe A. 2016 Reverse phenotyping comes of age. Mol. Genet. Metab. 118, 230–231.CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  1. 1.Medical Genetics, Department of Medicine and SurgeryUniversity of ParmaParmaItaly
  2. 2.TOMA, Advanced Biomedical Assays S.p.A., Busto ArsizioBusto ArsizioItaly
  3. 3.Medical GeneticsUniversity Hospital of ParmaParmaItaly

Personalised recommendations