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New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder–Robinson X-linked recessive mental retardation syndrome
  1. G de Alencastro1,
  2. D E McCloskey2,
  3. S E Kliemann3,
  4. C M C Maranduba1,
  5. A E Pegg2,
  6. X Wang2,
  7. D R Bertola4,
  8. C E Schwartz5,
  9. M R Passos-Bueno1,
  10. A L Sertié1
  1. 1
    Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, Brazil
  2. 2
    Department of Cellular and Molecular Pathology, Penn State University College of Medicine, Hershey, Pennsylvania, USA
  3. 3
    Associação Cruz Verde, São Paulo, Brazil
  4. 4
    Instituto da Criança do Hospital das Clínicas, Faculdade de Medicina, USP, São Paulo, Brazil
  5. 5
    J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, South Carolina, USA
  1. Dr A Laurato Sertié, Rua do Matão 277, Depto. Genética e Biologia Evolutiva, Instituto de Biociências, USP, São Paulo, SP, 05508-900, Brazil; asertie{at}


We report the identification of a novel mutation at a highly conserved residue within the N-terminal region of spermine synthase (SMS) in a second family with Snyder–Robinson X-linked mental retardation syndrome (OMIM 309583). This missense mutation, p.G56S, greatly reduces SMS activity and leads to severe epilepsy and cognitive impairment. Our findings contribute to a better delineation and expansion of the clinical spectrum of Snyder–Robinson syndrome, support the important role of the N-terminus in the function of the SMS protein, and provide further evidence for the importance of SMS activity in the development of intellectual processing and other aspects of human development.

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  • Funding: This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), NICHD grant (HD26202) to CES, NIH grant (GM-26290) to AEP and, in part, by a grant from the South Carolina Department of Disabilities and Special Needs (SCDDSN).

  • Competing interests: None declared.

  • Patient consent: Obtained.

  • Ethics approval: The study was approved by the research ethics committee of the Institute of Biosciences, University of São Paulo, Brazil.