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A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome

Authors

  • Stefano Sartori,

    1. Department of Pediatrics, Pediatric Neurology Unit, University of Padua, Padua, Italy
    2. Department of Pediatrics, Rare Disease Laboratory, University of Padua, Padua, Italy
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  • Gabriella Di Rosa,

    1. Department of Medical and Surgical Pediatrics, Unit of Infantile Neuropsychiatry, University Hospital of Messina, Messina, Italy
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  • Roberta Polli,

    1. Department of Pediatrics, Rare Disease Laboratory, University of Padua, Padua, Italy
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  • Elisa Bettella,

    1. Department of Pediatrics, Rare Disease Laboratory, University of Padua, Padua, Italy
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  • Giovanni Tricomi,

    1. Department of Medical and Surgical Pediatrics, Unit of Infantile Neuropsychiatry, University Hospital of Messina, Messina, Italy
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  • Gaetano Tortorella,

    1. Department of Medical and Surgical Pediatrics, Unit of Infantile Neuropsychiatry, University Hospital of Messina, Messina, Italy
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  • Alessandra Murgia M.D., Ph.D.

    Corresponding author
    1. Department of Pediatrics, Pediatric Neurology Unit, University of Padua, Padua, Italy
    2. Department of Pediatrics, Rare Disease Laboratory, University of Padua, Padua, Italy
    • Department of Pediatrics, University of Padua, Via Giustiniani, 3, 35128 Padova, Italy.
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  • Stefano Sartori and Gabriella Di Rosa contributed equally to this work.

  • How to cite this article: Sartori S, Di Rosa G, Polli R, Bettella E, Tricomi G, Tortorella G, Murgia A. 2009. A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome. Am J Med Genet Part A 149A:232–236.

Abstract

Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures. © 2009 Wiley-Liss, Inc.

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